脂肪细胞因子衍生物对乳腺癌侵袭和转移的影响
摘要
肥胖是一个在全球范围内持续增加的公共健康问题,它不仅与胰岛素抵抗和2型糖尿病密切相关,而且也是患一些常见肿瘤的风险因素,如乳腺癌、子宫内膜癌、结肠直肠癌以及前列腺癌等。肥胖导致一些内源性激素分泌的改变,包括类固醇激素、胰岛素和IGF系统,这些激素能影响细胞分化和血管再生。近年发现,脂肪组织不仅是能量储存的场所,还是一个非常活跃的内分泌代谢器官,分泌多种多肽物质,即脂肪细胞因子,包括VEGF、HGF、LEP、TNF-α、HB-EGF、IL-6、抵抗素以及脂联素等等,它们与肿瘤尤其是乳腺癌的发生发展密切相关,但作用机制还未完全阐明,绝大多数均停留在流行病学水平,实验证据较少。
恶性肿瘤的侵袭和转移是一个复杂过程,其中降解细胞外基质是重要的一步。众多研究证实,MMPs与细胞外基质的降解密切相关。MMPs是一类具有锌离子依赖性的蛋白水解酶超家族,不同成员降解ECM中的不同成分。几乎所有的ECM成分均能被MMPs降解。TIMPs的功能主要是抑制MMPs的活性,其作用方式较为复杂,大多数情形下二者以1:1的比例结合成复合物,使MMPs活性丧失。众多研究表明,肿瘤中TIMPs的表达明显降低。
鉴于目前关于脂肪细胞因子抵抗素抑制肿瘤细胞侵袭和转移作用的研究尚未见到报道,本文首次利用与人抵抗素具有同源性的抵抗素13肽,研究抵抗素对人乳腺癌细胞体内体外侵袭转移及相关机制的影响。本研究采用MTT法和平板克隆形成实验测定抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内,按照时间依赖方式和剂量依赖方式抑制MDA-MB-231乳腺癌细胞的增殖和克隆形成,即随着药物作用时间的延长和药物剂量的增加,对肿瘤细胞增殖作用的抑制也增强。应用Transwell模型重建基底膜实验,发现抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内能按照剂量依赖方式降低肿瘤细胞的侵袭能力。同时应用Transwell小室实验和划痕迁移实验,证实抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内,也能按照剂量依赖方式降低肿瘤细胞的迁移运动能力。采用粘附实验发现抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内的粘附能力也受到抑制。随后应用流式细胞仪测得抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内,均能诱导肿瘤细胞凋亡,但是在其最高浓度10μg/ml作用下其凋亡率也低于10%,由此我们可以得出抵抗素13肽在一定程度通过诱导肿瘤细胞凋亡来降低肿瘤细胞的增殖、粘附、侵袭和迁移能力,但结果证明这不是最主要的途径。接下来,在本研究中应用明胶酶谱法和Western blotting法分析抵抗素13肽对肿瘤细胞分泌MMP-2和MMP-9及其组织抑制物TIMP-1和TIMP-2的影响,发现抵抗素13肽在50ng/ml及以上浓度时,MMP-2蛋白活性形式及酶原表达量以及MMP-9蛋白活性形式表达量随浓度的升高而下降,而它们的组织抑制物TIMP-1和TIMP-2的蛋白表达量则随浓度的升高而升高。由此我们可以推测抵抗素13肽对肿瘤细胞侵袭及粘附能力的降低可能是通过调节基质金属蛋白酶及抑制物的表达,保护基底膜不受破坏来实现的。最后,本研究还通过重建肿瘤模型进行抵抗素13肽体内抗癌作用研究,发现抵抗素13肽在体内也能抑制实体瘤的生长,除了肝脏有轻微的炎症外,并对其它的脏器并未产生毒理作用。解剖也没有看到预期中的卵巢囊肿现象的发生。
另外,脂联素是作为目前发现的唯一抗血管生成的一种脂肪细胞因子,在流行病学以及临床调查研究发现,与乳腺癌的发生密切相关,在血清中的浓度与乳腺癌的发生呈负相关。本研究应用人脂联素重组体观测脂联素在乳腺癌的体外侵袭迁移作用,与流行病学调查结果一致。脂联素在体外能够抑制乳腺癌细胞的增殖、粘附、侵袭以及迁移能力,同时按照剂量依赖方式降低MMP-2和-9的活性及蛋白表达量的水平,以及按照同样方式增加TIMP-1和-2的蛋白表达水平。由此,推测脂联素重组体抑制肿瘤细胞侵袭过程可能是通过调节MMPs及其抑制剂来实现的。
综上所述,本文首次将脂肪细胞因子衍生物抵抗素13肽用于抗肿瘤侵袭迁移研究,发现抵抗素13肽在体内外抑制肿瘤细胞的增殖、粘附和侵袭迁移能力,并初步认识其作用机制。同时在细胞水平证实另一种脂肪细胞因子衍生物脂联素重组体也能抑制肿瘤细胞的粘附及侵袭迁移能力。这有利于从脂肪细胞因子抗肿瘤侵袭迁移作用的角度,拓展脂肪细胞因子抗肿瘤及治疗其他疾病机制研究的范围,并为开发脂肪细胞因子类药物抑制肿瘤侵袭转移等疾病提供新的理论依据。
Obesity is a serious health problem, as it is not only associated with a variety of metabolic disorders but also with an increased risk of developing cancer. More specifically, obesity has been identified as a risk factor for breast cancer. Unfortunately, the mechanism by which obesity increases cancer risk is not yet known. Insights into the mechanism(s) through which obesity increases the risk of cancer are urgently needed to develop new strategies for the prevention and treatment of certain cancers. Current epidemiologic and experimental studies of the obesity cancer association focus on the role of increased adipose tissue, particularly the increase in circulating adipocyte-derived factors (adipokines). Multiple factors from adipose tissue, such as leptin, adiponectin, cytokines, and other secreted products, influence processes involved in carcinogenesis.
Metastasis is one of the major causes of mortality in breast cancer patients and occurs as a complex multistep process that involves cancer cell adhesion, invasion, and migration. In the multiple stages of these processes, the degradation of environmental barriers, such as the extracellular matrix (ECM) and basement membrane, is the initial step, and several proteolytic enzymes participate in the degradation of these barriers. Among these enzymes, MMPs play a major role. TIMPs are natural inhibitors of MMPs found in most tissues and body fluids. By inhibiting MMPs activities, they participate in tissue remodeling of the ECM and inhibit tumor invasion and metastasis. Numerous investigations have pointed out that the MMPs and TIMPs play an important role in the invasion and metastasis of cancers. In addition, MMP-2 and MMP-9 degrade components of the basement membrane and are strongly implicated in the invasion and metastasis of malignant tumors. Therefore, the inhibition of invasion mediated by MMP-2 and MMP-9 may be crucial for the inhibition of cancer metastasis. Recent clinical studies have shown that MMP activity is required for rapidly proliferating and invading tumors rather than for already established tumors. Thus, the inhibition of MMP activity is important for the prevention of early stage carcinogenesis, particularly the tumor promotion process.
Resistin is known as an adipocyte-specific secretory cysteine-rich hormone that can cause insulin resistance and decrease adipocyte differentiation. Many aspects studies have provided evidence of a role of resistin in inflammatory processes that may be involved in atherosclerosis. The aim of this study was to elucidate the potential of resistin-13-peptide as an inhibitor of MMP-2 and MMP-9 activities using gelatin zymography, and to present the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 proteins using western blotting. We also investigated the influence of resistin-13-peptide on cancer cell viability, colony formation, adhesion, invasion, and animal experiment using MDA-MB-231 breast cancer cells. In results, Resistin-13-peptide inhibited MDA-MB-231 cells growth and colony formation in dose-dependent and time-dependent manners. Meanwhile, the invasive and adhesive abilities of MDA-MB-231 cells were yet cut down by resistin-13-peptide in dose-dependent manners. Resistin-13-peptide decreased the gelatinolytic activities of both MMP-2 and MMP-9, enhanced the protein expression of TIMP-1 and TIMP-2, which were secreted from the MDA- MB-231 cells. The animal experiments found the growth of tumors were repressed by resistin-13- peptide, which not injured other organs in the same time. Especially ovaries didn't have pathological changes yet. In conclusions, the treatment with resistin-13- peptide is effective in suppressing tumor proliferation, adhesion and invasion. The possible mechanism is down-regulation of MMPs and up-regulation of TIMPs.
In addition, adiponectin, a major adipose cytokine, plays a crucial role in the inhibition of metabolic syndrome by acting on such cell types as muscle cells and hepatocytes. Furthermore, evidence suggests that adiponectin may influence cancer pathogenesis. Previous studies have been reported on the potential link between breast cancer and adiponectin in the epidemiologic surveys. Low serum adiponectin levels may be a novel risk factor for breast cancer and study of adiponectin biology can provide new insights into the association of obesity with cancer risk. Since the mechanisms of action of adiponectin are not entirely clear, future studies are needed to fully elucidate the action of this hormone. In the present study, we investigated the influence of g-adiponectin, which is human adiponectin globular domain (104-247) recombinant protein, on cancer cell viability, adhesion, invasion and motility using MDA-MB-231 cells. Furthermore, we determined the potential effects of g-adiponectin on MMP-2 and MMP-9 activities using gelatin zymography, and to present the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 proteins and mRNA using western blotting and RT-PCR assays. In results, adiponectin recombinant inhibited MDA- MB-231 cells growth and colony formation in dose-dependent and time-dependent manners. Meanwhile, the invasive and adhesive abilities of MDA-MB-231 cells were yet cut down by adiponectin recombinant in dose-dependent manners. Adiponectin recombinant decreased the gelatinolytic activities of both MMP-2 and MMP-9, enhanced the protein expression of TIMP-1 and TIMP-2, which were secreted from the MDA- MB-231 cells. This was testified in mRNA level in the same time. In conclusions, the treatment with adiponectin recombinant is effective in suppressing tumor proliferation, adhesion and invasion. The possible mechanism is down-regulation of MMPs and up-regulation of TIMPs.
恶性肿瘤的侵袭和转移是一个复杂过程,其中降解细胞外基质是重要的一步。众多研究证实,MMPs与细胞外基质的降解密切相关。MMPs是一类具有锌离子依赖性的蛋白水解酶超家族,不同成员降解ECM中的不同成分。几乎所有的ECM成分均能被MMPs降解。TIMPs的功能主要是抑制MMPs的活性,其作用方式较为复杂,大多数情形下二者以1:1的比例结合成复合物,使MMPs活性丧失。众多研究表明,肿瘤中TIMPs的表达明显降低。
鉴于目前关于脂肪细胞因子抵抗素抑制肿瘤细胞侵袭和转移作用的研究尚未见到报道,本文首次利用与人抵抗素具有同源性的抵抗素13肽,研究抵抗素对人乳腺癌细胞体内体外侵袭转移及相关机制的影响。本研究采用MTT法和平板克隆形成实验测定抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内,按照时间依赖方式和剂量依赖方式抑制MDA-MB-231乳腺癌细胞的增殖和克隆形成,即随着药物作用时间的延长和药物剂量的增加,对肿瘤细胞增殖作用的抑制也增强。应用Transwell模型重建基底膜实验,发现抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内能按照剂量依赖方式降低肿瘤细胞的侵袭能力。同时应用Transwell小室实验和划痕迁移实验,证实抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内,也能按照剂量依赖方式降低肿瘤细胞的迁移运动能力。采用粘附实验发现抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内的粘附能力也受到抑制。随后应用流式细胞仪测得抵抗素13肽在5ng/ml～10μg/ml质量浓度范围内,均能诱导肿瘤细胞凋亡,但是在其最高浓度10μg/ml作用下其凋亡率也低于10%,由此我们可以得出抵抗素13肽在一定程度通过诱导肿瘤细胞凋亡来降低肿瘤细胞的增殖、粘附、侵袭和迁移能力,但结果证明这不是最主要的途径。接下来,在本研究中应用明胶酶谱法和Western blotting法分析抵抗素13肽对肿瘤细胞分泌MMP-2和MMP-9及其组织抑制物TIMP-1和TIMP-2的影响,发现抵抗素13肽在50ng/ml及以上浓度时,MMP-2蛋白活性形式及酶原表达量以及MMP-9蛋白活性形式表达量随浓度的升高而下降,而它们的组织抑制物TIMP-1和TIMP-2的蛋白表达量则随浓度的升高而升高。由此我们可以推测抵抗素13肽对肿瘤细胞侵袭及粘附能力的降低可能是通过调节基质金属蛋白酶及抑制物的表达,保护基底膜不受破坏来实现的。最后,本研究还通过重建肿瘤模型进行抵抗素13肽体内抗癌作用研究,发现抵抗素13肽在体内也能抑制实体瘤的生长,除了肝脏有轻微的炎症外,并对其它的脏器并未产生毒理作用。解剖也没有看到预期中的卵巢囊肿现象的发生。
另外,脂联素是作为目前发现的唯一抗血管生成的一种脂肪细胞因子,在流行病学以及临床调查研究发现,与乳腺癌的发生密切相关,在血清中的浓度与乳腺癌的发生呈负相关。本研究应用人脂联素重组体观测脂联素在乳腺癌的体外侵袭迁移作用,与流行病学调查结果一致。脂联素在体外能够抑制乳腺癌细胞的增殖、粘附、侵袭以及迁移能力,同时按照剂量依赖方式降低MMP-2和-9的活性及蛋白表达量的水平,以及按照同样方式增加TIMP-1和-2的蛋白表达水平。由此,推测脂联素重组体抑制肿瘤细胞侵袭过程可能是通过调节MMPs及其抑制剂来实现的。
综上所述,本文首次将脂肪细胞因子衍生物抵抗素13肽用于抗肿瘤侵袭迁移研究,发现抵抗素13肽在体内外抑制肿瘤细胞的增殖、粘附和侵袭迁移能力,并初步认识其作用机制。同时在细胞水平证实另一种脂肪细胞因子衍生物脂联素重组体也能抑制肿瘤细胞的粘附及侵袭迁移能力。这有利于从脂肪细胞因子抗肿瘤侵袭迁移作用的角度,拓展脂肪细胞因子抗肿瘤及治疗其他疾病机制研究的范围,并为开发脂肪细胞因子类药物抑制肿瘤侵袭转移等疾病提供新的理论依据。
Obesity is a serious health problem, as it is not only associated with a variety of metabolic disorders but also with an increased risk of developing cancer. More specifically, obesity has been identified as a risk factor for breast cancer. Unfortunately, the mechanism by which obesity increases cancer risk is not yet known. Insights into the mechanism(s) through which obesity increases the risk of cancer are urgently needed to develop new strategies for the prevention and treatment of certain cancers. Current epidemiologic and experimental studies of the obesity cancer association focus on the role of increased adipose tissue, particularly the increase in circulating adipocyte-derived factors (adipokines). Multiple factors from adipose tissue, such as leptin, adiponectin, cytokines, and other secreted products, influence processes involved in carcinogenesis.
Metastasis is one of the major causes of mortality in breast cancer patients and occurs as a complex multistep process that involves cancer cell adhesion, invasion, and migration. In the multiple stages of these processes, the degradation of environmental barriers, such as the extracellular matrix (ECM) and basement membrane, is the initial step, and several proteolytic enzymes participate in the degradation of these barriers. Among these enzymes, MMPs play a major role. TIMPs are natural inhibitors of MMPs found in most tissues and body fluids. By inhibiting MMPs activities, they participate in tissue remodeling of the ECM and inhibit tumor invasion and metastasis. Numerous investigations have pointed out that the MMPs and TIMPs play an important role in the invasion and metastasis of cancers. In addition, MMP-2 and MMP-9 degrade components of the basement membrane and are strongly implicated in the invasion and metastasis of malignant tumors. Therefore, the inhibition of invasion mediated by MMP-2 and MMP-9 may be crucial for the inhibition of cancer metastasis. Recent clinical studies have shown that MMP activity is required for rapidly proliferating and invading tumors rather than for already established tumors. Thus, the inhibition of MMP activity is important for the prevention of early stage carcinogenesis, particularly the tumor promotion process.
Resistin is known as an adipocyte-specific secretory cysteine-rich hormone that can cause insulin resistance and decrease adipocyte differentiation. Many aspects studies have provided evidence of a role of resistin in inflammatory processes that may be involved in atherosclerosis. The aim of this study was to elucidate the potential of resistin-13-peptide as an inhibitor of MMP-2 and MMP-9 activities using gelatin zymography, and to present the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 proteins using western blotting. We also investigated the influence of resistin-13-peptide on cancer cell viability, colony formation, adhesion, invasion, and animal experiment using MDA-MB-231 breast cancer cells. In results, Resistin-13-peptide inhibited MDA-MB-231 cells growth and colony formation in dose-dependent and time-dependent manners. Meanwhile, the invasive and adhesive abilities of MDA-MB-231 cells were yet cut down by resistin-13-peptide in dose-dependent manners. Resistin-13-peptide decreased the gelatinolytic activities of both MMP-2 and MMP-9, enhanced the protein expression of TIMP-1 and TIMP-2, which were secreted from the MDA- MB-231 cells. The animal experiments found the growth of tumors were repressed by resistin-13- peptide, which not injured other organs in the same time. Especially ovaries didn't have pathological changes yet. In conclusions, the treatment with resistin-13- peptide is effective in suppressing tumor proliferation, adhesion and invasion. The possible mechanism is down-regulation of MMPs and up-regulation of TIMPs.
In addition, adiponectin, a major adipose cytokine, plays a crucial role in the inhibition of metabolic syndrome by acting on such cell types as muscle cells and hepatocytes. Furthermore, evidence suggests that adiponectin may influence cancer pathogenesis. Previous studies have been reported on the potential link between breast cancer and adiponectin in the epidemiologic surveys. Low serum adiponectin levels may be a novel risk factor for breast cancer and study of adiponectin biology can provide new insights into the association of obesity with cancer risk. Since the mechanisms of action of adiponectin are not entirely clear, future studies are needed to fully elucidate the action of this hormone. In the present study, we investigated the influence of g-adiponectin, which is human adiponectin globular domain (104-247) recombinant protein, on cancer cell viability, adhesion, invasion and motility using MDA-MB-231 cells. Furthermore, we determined the potential effects of g-adiponectin on MMP-2 and MMP-9 activities using gelatin zymography, and to present the expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 proteins and mRNA using western blotting and RT-PCR assays. In results, adiponectin recombinant inhibited MDA- MB-231 cells growth and colony formation in dose-dependent and time-dependent manners. Meanwhile, the invasive and adhesive abilities of MDA-MB-231 cells were yet cut down by adiponectin recombinant in dose-dependent manners. Adiponectin recombinant decreased the gelatinolytic activities of both MMP-2 and MMP-9, enhanced the protein expression of TIMP-1 and TIMP-2, which were secreted from the MDA- MB-231 cells. This was testified in mRNA level in the same time. In conclusions, the treatment with adiponectin recombinant is effective in suppressing tumor proliferation, adhesion and invasion. The possible mechanism is down-regulation of MMPs and up-regulation of TIMPs.
引文
1 全球760万人今年死于癌症,美国癌症协会,2007年12月17日
2 中国癌症预防与控制规划纲要(2004-2010)。中国肿瘤,2004,13(2):65-68
3 Liotta LA.Tumor invasion and metastases-role of the extracellular-Matrix:Rhoads Memorial Award lecture.Cancer Res,1986,46(1):1-7
4 Ray JM,Stetler-Stevenson WG.Gelatinase A activity directly modulates melanoma cell adhesion and spreading.EMBO J.1995,14(5):908-917
5 Chambers AF,Matrisian LM.Changing views of the role of matrix metallopro-teinases in metastasis.J Natl Cancer Inst.1997,89(17):1260-1270
6 Kahari VM,Saarialho-Kere U.Matrix metalloproteinases and their inhibitors in tumour growth and invasion.Ann Med.1999,31(1):34-45
7 Kleiner DE,Stetler-Stevenson WG.Matrix metalloproteinases and metastasis.Cancer Chemother Pharmacol.1999,43 Suppl:S42-S51
8 Nelson AR,Fingleton B,Rothenberg ML,et al.Matrix metalloproteinase:biologic activity and clinical implication.J Clin Oncol.2000,18(5):1135-11491
9 Hanemaaier R,Verheijen J H,Mayuire TM,et al.lncreasedgelatinase-A and gelatinase-B activities in mallignant vs benign breast tumors,lnt J Cancer.2000,86:204-207
10 Still K,Robson CN,Autzen P,et al.Localization and quantification of mRNA for matrix metalloproteinase-2(MMP-2) and tissue inhibitor of matrix metalloproteinase-2(TIMP-2) in human benign and malignant protatic tissue.Prostate.2000,42(1):18-25
11 Gong YI,Xu GM,Huang WD,et al.Expression of matrix metalloproteinases and the tissue inhibitors of metalloproteinases and their local invasiveness and metastasis in Chinese human pancreatic cancer.J Surg Oncol.2000,73(2):95-99
12 Dalberg K,Eriksson E,Enberg U,et al.Gelatinase A,membrane type 1 matrix metalloproteinase,and extracellular matrix metalloproteinase inducer mRNA expression:correlation with invasive growth of breast cancer.World J Surg.2000,24(3):334-340
13 Yoshimoto M,Itoh F,Yamamoto H,et al.Expression of MMP-7(PUMP-1)mRNA in human colorectal cancers.Int J Cancer.1993,54(4):614-618
14 Koshiba T,Hosotani R,Wada M,et al.Involvement of matrix metalloproteinase-2activity invasion and metastasis of pancreatic carcinoma. Cancer. 1998, 82 (4) :642-650
15 Somiari SB, Somiari RI, Heckman CM, et al. Circulating MMP2 and MMP9 in breast cancer — potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int J Cancer. 2006, 119(6):1403-1411
16 Pellikainen JM, Ropponen KM, Kataja VV, et al. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis. Clin Cancer Res.2004, 10(22): 7621-7628.
17 Tang Y, Nakada MT, Kesavan P, et al. Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases.Cancer Res. 2005, 65(8):3193-3199
18 Kurizaki T, Toi M, Tominaga T. Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma. Oncol Rep. 1998, 5(3):673-677
19 Wolk A, Gridley G, Svensson M, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control. 2001, 12(1):13—21.
20 Werner H, LeRoith D. The role of the insulin-like growth factor system in human cancer. Adv Cancer Res. 1996, 68:183-223
21 Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth.Endocr Rev. 2000, 21 (3):215-244
22 Kluge A, Zimmermann R, Munkel B, et al. Insulin-like growth factor I is involved in inflammation linked angiogenic processes after micro-embolisation in porcine heart. Cardiovasc Res. 1995, 29(3): 407-415
23 Youn BS, Min SS, Park KS, et al. The role of adipocytokines in adipocyte-related pathological processes. Drug News Perspect. 2004,17(5):293-298
24 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003,9(15):5699-5704
25 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004, 89(3):1102-11027
26 Manabe Y, Toda S, Miyazaki K, Sugihara H. Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions.J Pathol.2003, 201(2):221-228
27 Brakenhielm E, Veitonmaki N, Cao R, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004, 101(8):2476-2481
28 Leach RE, Romero R, Kim YM, et al. Pre-eclampsia and expression of heparin-binding EGF-like growth factor. Lancet. 2002, 360(9341): 1215-1219
29 Castellucci M, De Matteis R, Meisser A, et al. Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion. Mol Hum Reprod. 2000,6(10):951-958
30 Meisser A, Cameo P, Islami D, et al. Effects of interleukin-6 (IL—6) on cytotrophoblastic cells. Mol Hum Reprod. 1999, 5(11):1055-1058
31 Fujiuchi Y, Nagakawa O, Murakami K, Fuse H, Saiki I. Effect of hepatocyte growth factor on invasion of prostate cancer cell lines.Oncol Rep. 2003, 10(4):1001-1006
32 Lamszus K, Jin L, Fuchs A, et al. Scatter factor stimulates tumor growth and tumor angiogenesis in human breast cancers in the mammary fat pads of nude mice. Lab Invest. 1997, 76(3):339-353
33 Lee PP, Hwang JJ, Murphy G, Ip MM. Functional significance of MMP-9 in tumor necrosis factor-induced proliferation and branching morphogenesis of mammary epithelial cells. Endocrinology. 2000,141(10):3764-3773
34 Leek RD, Landers R, Fox SB, et al. Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma. Br J Cancer. 1998, 77(12):2246-2251
35 Arihiro K, Oda H, Kaneko M, Inai K. Cytokines facilitate chemotactic motility of breast carcinoma cells. Breast Cancer. 2000, 7(3) :221-230
36 Salgado R, Junius S, Benoy I, et al. Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer. 2003,103(5):642-646
37 Loi S, Milne RL, Friedlander ML, et al. Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 2005, 14(7):1686-1691
38 Youn BS, Min SS, Park KS, et al. The role of adipocytokines in adipocyte-related pathological processes. Drug News Perspect. 2004,17(5):293-298
39 Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes.Nature,2001,409(6818):307-312
40 Hou WK,Xian YX,Zhang L,et al.Influence of blood glucose on the expression of glucose trans-porter proteins 1 and 3 in the brain of diabetic rats.Chin Med J(Engl).2007,120(19):1704-1709
41 Guarini 1.Temponi M.Edwards GM,ET AL.In virtro differentiation and antigenic changes in human melanoma cells.Cancer Immunal Immunther,1987,30,262-268
42 Hanemaaier R,Verheijen J H,Mayuire TM,et al.lncreasedgelatinase-A and gelatinase-B activities in mallignant vs benign breast tumors.Int J Cancer.2000,86:204-207
43 Laud K,Gourdou I,Pessemesse L,et al.Identification of leptin receptors in human breast cancer:functional activity in the T47-D breast cancer cell line.Mol Cell Endocrinol.2002,188(1-2):219-226
44 Dieudonne MN,Machinal-Quelin F,Serazin-Leroy V,et al.Leptin mediates a proliferative response in human MCF7 breast cancer cells.Biochem Biophys Res Commun.2002,293(1):622-628
45 Mu H,Ohashi R,Yan S,et al.Adipokine resistin promotes in vitro angiogenesis of human endothelial cells.Cardiovasc Res.2006 Apr 1;70(1):146-157
46 Calabro P,Samudio I,Willerson JT,Yeh ET.Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways.Circulation.2004,110(21):3335-3340
47 Saiki I.Cell adhesion molecules and cancer metastasis.Jpn J Pharmacol,1997,75(3):215-243
48 郝光荣,姚明,朱德生。免疫缺陷动物。见:郝光荣,主编。实验动物学。上海:第二军医大学出版社,第一版,2000,200-202;
49 司徒镇强,吴军正。裸鼠移植瘤动物模型。见:司徒镇强,吴军正,主编。细胞培养。陕西:世界图书出版社,第一版,1996,144-147
50 Maeda k,Okubo K,Shimomura I,et al.CDNA cloning and expression of a novel adipose specific collagen-like factor,apM1(Adipose Most Abundant Oene Transcript 1).Biochem.Biophys Res Commun,1996,221:286 298
51 Chandran M,Phillips SA,Ciaraldi T,et al.idiponectin:more than just another fat cell hormone? Diabetes Care.2003,6(8):2442-2450
52 Tsao TS,Murrey HE,Hug C,et al.Oligomerization state-dependent activation of NF-κB signaling pathway by adipocyte complement-related protein of 30kDa(icrp30).J.Biol.them,2002,277(33):29359-29362
53 Guang W, Jin Wang, Christopher Hug, et al. A family of Acrp30/adiponectin structural and functional paralogs. PNAS. 2004, 101(28):10302-10307
54 Yaraauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423(6941):762-769
55 Kharroubi I, Rasschaert J, Eizirik DL, Cnop M. Expression of adiponectin receptors in pancreatic beta cells. Biochem Biophys Res Commun. 2004, 312 (4):1118-1122
56 Takahata C, Miyoshi Y, Irahara N, et al. Demonstration of adiponectin receptors 1 and 2 mRNA expression in human breast cancer cells. Cancer Lett. 2007, 250(2):229-236
57 Dieudonne MN, Bussiere M, Dos Santos E, et al. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun. 2006, 345(1) :271-279
58 Kang JH, Lee YY, Yu BY, et al. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch Pharm Res. 2005,28(11):1263-1269.
59 Harvie M, Howell A. Energy balance adiposity and breast cancer-energy restriction strategies for breast cancer prevention. Obes Rev. 2006 ,7(1):33-47
60 Chen DC, Chung YF, Yeh YT, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2006, 237(1) :109—114
61 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk, J Clin Endocrinol Metab. 2004 , 89(3):1102-1107
62 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003,9(15):5699-5704
63 Rose DP, Komninou D, Stephenson GD. Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev. 2004 , 5(3):153-165
64 Petridou E, Mantzoros C, Koukoulomatis P,et al. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinoi Metab. 2003 , 88(3):993-997
65 Dal Maso L , Augustin LS, Karalis A, et al. Circulating adiponectin and endometrial cancer risk. J Clin Endocrinoi Metab. 2004 , 89(3):1160-1163
66 IshikawaM, Kitayama J, Kazama S, et al. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005, 11(2 Pt 1):466-472
67 Goktas S, Yilraaz MI, Caglar K, et al. Prostate cancer and adiponectin.Urology. 2005, 65(6):1168-1172
68 Freedland SJ, Sokoll LJ, Platz EA, et al. Association between serum adiponectin, and pathological stage and grade in men undergoing radical prostatectomy. J Urol. 2005, 174(4 Pt 1):1266-1270
69 Wei EK, Giovannucci E, Fuchs CS, et al. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst. 2005, 97(22):1688-1694
70 Petridou E, Mantzoros CS, Dessypris N, et al. Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer. 2006, 94(1) : 156-60.
71 Liotta LA. Tumor invasion and metastases: role of the basement membrane.Am J Pathol. 1984, 117(3) :339-348
72 Hanemaaier R, Verheijen J H, Mayuire TM, et al. Increasedgelatinase-A and gelatinase-B activities in mallignant vs benign breast tumors. Int J Cancer. 2000, 86: 204-207
73 Kaaks R, Toniolo P, Akhmedkhanov A, et al. Serum C-peptide,insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst. 2000 ,92(19):1592-1600
74 Yokata T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.Blood. 2000, 96(5):1723-1732
75 Wang Y, Lam KS, Xu LY, et al. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem. 2005, 280(18): 18341-18347
76 Kang JH, Yu BY, Youn DS. Relationship of serum adiponectin and resist in levels with breast cancer risk. J Korean Med Sci. 2007, 22(1):117-121
1 The World Health Organization MONICA Project(monitoring trends and determinants in cardiovascular disease):a major international collaboration.WHO MONICA Project Principal Investigators.J Clin Epidemiol. 1988, 41(2): 105-114.
2 Kopelman PG. Obesity as a medical problem. Nature. 2000, 404(6778):635-643.
3 Wolk A, Gridley G, Svensson M, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control. 2001, 12(1):13-21
4 Bergstrom A, Pisani P, Tenet V, Wolk A, Adami HO. Overweight as an avoidable cause of cancer in Europe. Int J Cancer. 2001, 91(3) :421-430
5 Pan SY, Johnson KC, Ugnat AM, et al. Canadian Cancer Registries Epidemiology Research Group. Association of obesity and cancer risk in Canada. Am J Epidemiol. 2004, 159(3):259-268
6 Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity,and mortality from cancer in a prospectively studied cohort of U.S.adults. N Engl J Med. 2003, 348(17):1625-238
7 Werner H, LeRoith D. The role of the insulin-like growth factor system in human cancer. Adv Cancer Res. 1996, 68:183-223
8 Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth.Endocr Rev. 2000
9 Kluge A, Zimmermann R, Munkel B, et al. Insulin-like growth factor I is involved in inflammation linked angiogenic processes after microembolisation in porcine heart. Cardiovasc Res. 1995,29(3):407-415
10 Youn BS, Min SS, Park KS, et al. The role of adipocytokines in adipocyte-related pathological processes. Drug News Perspect. 2004,17(5) :293-298.
11 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003, 9(15):5699-56704
12 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004, 89(3):1102-1107
13 Manabe Y, Toda S, Miyazaki K, Sugihara H. Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions.J Pathol.2003, 201(2):221-228
14 Palmqvist R, Stattin P, Rinaldi S, et al. Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: a prospective study in northern Sweden. Int J Cancer. 2003, 107(1):89-93
15 Giovannucci E. Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr. 2001, 131(11 Suppl):3109S-3120S
16 Schoen RE, Tangen CM, Kuller LH, et al. Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst.1999, 91(13):1147-1154
17 Lawlor DA, Smith GD, Ebrahim S. Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women's Heart and Health Study. Cancer Causes Control. 2004, 15(3) :267-275
18 Kaaks R. Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control. 1996, 7(6):605-625
19 Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev. 2002, 11(12):1531-1543
20 Hammarsten J, Hogstedt B. Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. Eur J Cancer. 2005, 41(18):2887-2895
21 McCarty MF. Chronic activation of AMP-activated kinase as a strategy for slowing aging. Med Hypotheses. 2004, 63(2):334-339
22 Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D,Adami HO. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer. 1997, 76(9):1115-1118
23 Bohlke K, Cramer DW, Trichopoulos D, Mantzoros CS. Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiology. 1998, 9(5):570-3.
24 Bruning PF, Van Doom J, Bonfrer JM, Van Noord PA, Korse CM, Linders TC, Hart AA. Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. Int J Cancer.1995, 62(3):266-70.
25 Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B,Rosner B, Speizer FE, Pollak M. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998,351(9113):1393-6.
26 Kaulsay KK, Ng EH, Ji CY, et al. Serum IGF-binding protein-6 and prostate specific antigen in breast cancer. Eur J Endocrinol. 1999,140(2):164-168
27 Ayabe T, Tsutsumi O, Sakai H, et al. Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer. Endocr J. 1997, 44(3):419-424
28 Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science. 1998,279(5350): 563-566
29 Ma J, Pollak MN, Giovannucci E, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst. 1999,91(7):620-625
30 Renehan AG, Jones J, Potten CS, et al. Elevated serum insulin-like growth factor (IGF)-II and IGF binding protein-2 in patients with colorectal cancer. Br J Cancer. 2000, 83(10):1344-1350
31 Manousos O, Souglakos J, Bosetti C, et al. IGF-I and IGF—II in relation to colorectal cancer. Int J Cancer. 1999, 83(1):15-17
32 Lee DY, Kim SJ, Lee YC. Serum insulin-like growth factor (IGF)-I and IGF-binding proteins in lung cancer patients. J Korean Med Sci. 1999,14(4):401-404
33 Yu H, Spitz MR, Mistry J, et al. Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis. J Natl Cancer Inst. 1999, 91(2):151-156
34 Rose DP. Diet, hormones, and cancer. Annu Rev Public Health. 1993, 14:1-17
35 Bulun SE, Mahendroo MS, Simpson ER. Aromatase gene expression in adipose tissue: relationship to breast cancer. J Steroid Biochem Mol Biol. 1994, 49(4-6): 319-26
36 Barbieri RL, Makris A, Randall RW, et al. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab. 1986, 62(5) :904-910
37 Bernstein L, Ross RK. Endogenous hormones and breast cancer risk.Epidemiol Rev. 1993, 15(1) :48-65
38 Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab. 2000, (8):327-332.
39 Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue.Nature. 1994, 372(6505):425-432
40 Miczke A, Pupek-Musialik D. Leptin and obesity. Pol Merkur Lekarski.2000, 8(44): 109-112
41 Nakata M, Yada T, Soejima N, Maruyama I. Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes. 1999, 48(2):426-429
42 Hu X, Juneja SC, Maihle NJ, Cleary MP. Leptin—a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst. 2002, 94(22):1704-1711
43 Magoffin DA, Weitsman SR, Aagarwal SK, Jakimiuk AJ. Leptin regulation of aromatase activity in adipose stromal cells from regularly cycling women. Ginekol Pol. 1999, 70(1):1-7
44 Cleary MP, Juneja SC, Phillips FC, et al. Leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db) female mice do not develop oncogene-induced mammary tumors. Exp Biol Med (Maywood). 2004,229(2):182-193
45 O' brien SN, Welter BH, Price TM. Presence of leptin in breast cell lines and breast tumors. Biochem Biophys Res Commun. 1999, 259(3): 695-8.
46 Mantzoros CS, Bolhke K, Moschos S, Cramer DW. Leptin in relation to carcinoma in situ of the breast: a study of pre-menopausal cases and controls. Int J Cancer. 1999, 80(4):523-526
47 Petridou E, Papadiamantis Y, Markopoulos C, et al. Leptin and insulin growth factor I in relation to breast cancer (Greece). Cancer Causes Control. 2000, 11 (5):383-388
48 Ozet A, Arpaci F, Yilmaz MI, et al. Effects of tamoxifen on the serum leptin level in patients with breast cancer. Jpn J Clin Oncol. 2001,31(9):424-427.
49. Comings DE, Gade-Andavolu R, Cone LA, et al. A multigene test for the risk of sporadic breast carcinoma. Cancer. 2003, 97(9):2160-2170
50 Liu Z, Uesaka T, Watanabe H, Kato N. High fat diet enhances colonic cell proliferation and carcinogenesis in rats by elevating serum leptin.Int J Oncol. 2001, 19(5):1009-1014
51 Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ,Peppelenbosch MP. Leptin is a growth factor for colonic epithelial cells.Gastroenterology. 2001, 121 (1):79-90
52 Petridou E, Belechri M, Dessypris N, et al. Leptin and body mass index in relation to endometrial cancer risk. Ann Nutr Metab. 2002, 46(3-4) :147-151
53 Yuan SS, Tsai KB, Chung YF, et al. Aberrant expression and possible involvement of the leptin receptor in endometrial cancer. Gynecol Oncol.2004, 92(3):769-775
54 Chan TF, Su JH, Chung YF, et al. Decreased serum leptin levels in women with uterine leiomyomas. Acta Obstet Gynecol Scand. 2003, 82(2): 173— 176
55 Huang KC, Chuang LM, Chen CY, et al. Serum leptin and leptin receptor isoforms in omental adipose tissue of nondiabetic women undergoing gy necologic surgery for benign disease. J Formos Med Assoc, 2000, 99(11):839-843.
56 Remsberg KE, Talbe tt EO, Zberowski JV, et al. Evidence for competing efects of body mass, hyperinsulinemia, insulin resistance, an dandrogens on leptin levels among lean, overweight, and obe se women with polycystic ovary syndrome. Fertil Steril, 2002, 78(3): 479-486
57 Stattin P, Soderbe rg S, Hallman s G, et al. Leptin is associated with increased prostate can cer risk: a nested case-referent study. J Clin Endocrinol Metab, 2001, 86(3): 1341—1345.
58 Chang S, Humting SD, Contois JH, et al. Leptin and prostate cancer. Prostate, 2001, 46(1): 62-67.
59 Nakao T, Hino M , Yamane T, et al. Expression of the leptin receptor in human leukaemic blast cells. Br J Haematol, 1998, 102(3): 740-745.
60 Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita M. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem (Tokyo). 1996, 120(4):803-12.
61 Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996, 271(18):10697-10703.
62 Scherer PE, Williams S, FoglianoM, et al. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995,270(45):26746-26749.
63 Pineiro R, Iglesias MJ, Gallego R, et al. Adiponectin is synthesized and secreted by human and murine cardiomyocytes. FEBS Lett. 2005,579(23):5163-5169.
64 Chen J, Tan B, Karteris E, et al. Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia. 2006, 49(6):1292-1302.
65 Takahashi M, AritaY, YamagataK, et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord.2000, 24(7) :861-868.
66 Kissebah AH, Sonnenberg GE, Myklebust J, et al. Quantitative trait locion chromosomes 3 and 17 influence phenotypes of the metabolic syndrome.Proc Natl Acad Sci U S A. 2000, 97(26):14478-14483.
67 Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.Blood. 2000, 96(5): 1723-1732.
68 Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin.Circulation. 1999, 100(25):2473-2476.
69 Ouchi N, Kihara S, Arita Y, et al.. Adipocyte-derived plasma protein,adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation.2001, 103(8):1057-1063.
70 Wong GW, Wang J, Hug C, et al. A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci U S A. 2004,101 (28):10302-10307.
71 Tsao TS, Murrey HE, Hug C, et al. Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30). J Biol Chem. 2002,277(33): 29359-29362.
72 Peake PW, Kriketos AD, Campbell LV, et al. The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals. Eur J Endocrinol. 2005, 153(3):409-417.
73 Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005, 26(3):439-451
74 Fruebis J, Tsao TS, Javorschi S, et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A. 2001, 98(4):2005-2010
75 Waki H, Yamauchi T, Kamon J, et al. Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endocrinology. 2005, 146(2):790-796.
76 Goldstein BJ, Scalia R. Adiponectin: A novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab. 2004,89(6):2563-2568.
77 Tsao TS, Tomas E, Murrey HE, et al. Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. J Biol Chem.2003, 278(50):50810-50817.
78 Tomas E, Tsao TS, Saha AK, et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci U S A. 2002, 99(25):16309-16313.
79 Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med. 2001, 7(8) :947-953.
80 Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. J Biol Chem. 2003, 278(11): 9073-9085.
81 Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem. 2004, 279(13):12152-12162.
82 Fisher FF, Trujillo ME, Hanif W, et al. Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia. 2005,48(6):1084-1087.
83 Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423(6941):762-769.
84 Kharroubi I, Rasschaert J, Eizirik DL, Cnop M. Expression of adiponectin receptors in pancreatic beta cells. Biochem Biophys Res Commun. 2003, 312(4):1118-1122.
85 Miyazaki T, Bub JD, Uzuki M, Iwamoto Y. Adiponectin activates c-Jun NH2-terminal kinase and inhibits signal transducer and activator of transcription 3. Biochem Biophys Res Commun. 2005, 333(1) :79-87.
86 Tsuchida A, Yamauchi T, Ito Y, et al. Insulin/Foxol pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity.J Biol Chem. 2004, 279(29):30817-30822.
87 Inukai K, Nakashima Y, Watanabe M, et al. Regulation of adiponectin receptor gene expression in diabetic mice. Am J Physiol Endocrinol Metab.2005, 288(5):E876-82.
88 Oana F, Takeda H, Hayakawa K, Matsuzawa A, et al. Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin. Metabolism. 2005, 54(8):995-1001.
89 Tsuchida A, Yamauchi T, Takekawa S, et al. Peroxisome proliferator-activated receptor (PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue:comparison of activation of PPARalpha, PPARgamma, and their combination.Diabetes. 2005, 54(12):3358-3370.
90 Kaltenbach S, Staiger H, Weisser M, et al. Adiponectin receptor gene expression in human skeletal muscle cells is not regulated by fibrates and thiazolidinediones. Int J Obes (Lond). 2005, 29(7):760-765.
91 Adachi Y, Takeuchi T, Sonobe H, Ohtsuki Y. An adiponectin receptor,T-cadherin, was selectively expressed in intratumoral capillary endothelial cells in hepatocellular carcinoma: possible cross talk between T-cadherin and FGF-2 pathways. Virchows Arch. 2006, 448(3):311-318.
92 Dal Maso L, Augustin LS, Karalis A, et al. Circulating adiponectin and endometrial cancer risk. J Clin Endocrinol Metab. 2004,89(3): 1160-1163.
93 Petridou E, Mantzoros C, Dessypris N, et al. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinol Metab. 2003, 88(3):993-997.
94 Alvarez BV, Johnson DE, Sowah D, et al. Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy. J Physiol. 2007, 579(Pt 1): 127-145.
95 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004, 89(3):1102-1107.
96 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003,9(15):5699-5704.
97 Chen DC, Chung YF, Yeh YT, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2006, 237(1): 09-14.
98 Wei EK, Giovannucci E, Fuchs CS, et al. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study, J Natl Cancer Inst. 2005, 97(22) :1688-94.
99 Otake S, Takeda H, Suzuki Y, et al. Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance. Clin Cancer Res. 2005, 11(10):3642-6.
100 Ishikawa M, Kitayama J, Kazama S, et al. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005, 11(2 Pt 1):466-72.
101 Freedland SJ, Sokoll LJ, Platz EA, et al. Association between serum adiponectin, and pathological stage and grade in men undergoing radical prostatectomy. J Urol. 2005, 174(4 Pt 1):1266-70.
102 Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S, Bedir S. Prostate cancer and adiponectin. Urology. 2005, 65(6):1168-72.
103 Petridou E, Mantzoros CS, Dessypris N, et al. Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer. 2006, 94(1):156-60.
104 Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.Blood. 2000, 96(5): 1723-32.
105 Kang JH, Lee YY, Yu BY, et al. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch Pharm Res. 2005,28(11): 1263-9.
106 Dieudonne MN, Bussiere M, Dos Santos E, et al. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun. 2006, 345(1):271-9.
107 Bub JD, Miyazaki T, Iwamoto Y. Adiponectin as a growth inhibitor in prostate cancer cells. Biochem Biophys Res Commun. 2006, 340(4):1158-66.
108 Brakenhielm E, Veitonmaki N, et al. Adiponectin-induced antiangio-genesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004, 101(8): 2476-81.
109 Manabe Y, Toda S, Miyazaki K, Sugihara H. Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions. J Pathol.2003, 201(2):221-228
1 Maeda k,Okubo K,Shimomura I,et al.CDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (Adipose Most Abundant Gene Transcript 1). Biochem. Biophys Res Commun, 1996,221:286-298.
2 Chandran M, Phillips SA, Ciaraldi T, et al. Adiponectin: more than just another fat cell hormone? Diabetes Care. 2003, 6(8): 2442-50.
3 Tsao TS, Murrey HE, Hug C, et al. Oligomerizat'ion state-dependent activation of NF-κ B signaling pathway by adipocyte complement-related protein of 30kDa(Acrp30). J.Biol. Chem, 2002, 277(33): 29359-29362.
4 GuangW, Jin Wang, Christopher Hug, et al. A family of Acrp30/adiponectin structural and functional paralogs. PNAS. 2004,101 (28): 10302-10307.
5 Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423(6941) :762-9.
6 Kharroubi I, Rasschaert J, Eizirik DL, Cnop M. Expression of adiponectin receptors in pancreatic beta cells. Biochem Biophys Res Commun. 2004 ,312 (4): 1118-22.
7 Harvie M, Howell A. Energy balance adiposity and breast cancer-energy restriction strategies for breast cancer prevention. Obes Rev. 2006 ,7(1):33-47.
8 Chen DC, Chung YF, Yeh YT, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2005 Jul 11.
9 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004 , 89(3):1102-7.
10 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003,9(15):5699-704.
11 Kang JH, Lee YY, Yu BY, et al. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch Pharm Res. 2005,28(11):1263-9.
12 Rose DP, Komninou D, Stephenson GD. Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev. 2004 , 5(3):153-65.
13 Petridou E, Mantzoros C, Koukoulomatis P, et al. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinol Metab. 2003 , 88(3):993-7.
14 Dal Maso L , Augustin LS, Karalis A, et al. Circulating adiponectin and endometrial cancer risk. J Clin Endocrinol Metab. 2004 ,89(3): 1160-3.
15 Chen HS, Chan TF, Chung YF, et al. Aberrant serum adiponectin levels in women with uterine leiomyomas. Gynecol Obstet Invest. 2004,58(3):160-3
16 Ishikawa M, Kitayama J, Kazama S, et al. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005, 11(2 Pt 1):466-72.
17 Goktas S, Yilmaz MI, Caglar K, et al. Prostate cancer and adiponectin.Urology. 2005, 65(6):1168-72.
18 Freedland SJ, Sokoll LJ, Platz EA, et al. Association between serum adiponectin, and pathological stage and grade in men undergoing radical prostatectomy. J Urol. 2005, 174(4 Pt 1):1266-70.
19 Wei EK, Giovannucci E, Fuchs CS, et al. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst. 2005, 97(22):1688-94.
20 Otake S, Takeda H, Suzuki Y, et al. Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance. Clin Cancer Res.2005,11 (10): 3642-6.
21 Petridou E, Mantzoros CS, Dessypris N, et al. Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer. 2006, 94(1) :156-60.
22 Kaaks R, Toniolo P, Akhmedkhanov A, et al. Serum C-peptide,insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst. 2000 ,92(19): 1592-600.
23 Yokata T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myeiomonocytic progenitors and the functions of macrophages. Blood. 2000, 96(5):1723-32.
24 Wang Y, Lam KS, Xu LY, et al. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem. 2005, 280(18):18341-7.
2 中国癌症预防与控制规划纲要(2004-2010)。中国肿瘤,2004,13(2):65-68
3 Liotta LA.Tumor invasion and metastases-role of the extracellular-Matrix:Rhoads Memorial Award lecture.Cancer Res,1986,46(1):1-7
4 Ray JM,Stetler-Stevenson WG.Gelatinase A activity directly modulates melanoma cell adhesion and spreading.EMBO J.1995,14(5):908-917
5 Chambers AF,Matrisian LM.Changing views of the role of matrix metallopro-teinases in metastasis.J Natl Cancer Inst.1997,89(17):1260-1270
6 Kahari VM,Saarialho-Kere U.Matrix metalloproteinases and their inhibitors in tumour growth and invasion.Ann Med.1999,31(1):34-45
7 Kleiner DE,Stetler-Stevenson WG.Matrix metalloproteinases and metastasis.Cancer Chemother Pharmacol.1999,43 Suppl:S42-S51
8 Nelson AR,Fingleton B,Rothenberg ML,et al.Matrix metalloproteinase:biologic activity and clinical implication.J Clin Oncol.2000,18(5):1135-11491
9 Hanemaaier R,Verheijen J H,Mayuire TM,et al.lncreasedgelatinase-A and gelatinase-B activities in mallignant vs benign breast tumors,lnt J Cancer.2000,86:204-207
10 Still K,Robson CN,Autzen P,et al.Localization and quantification of mRNA for matrix metalloproteinase-2(MMP-2) and tissue inhibitor of matrix metalloproteinase-2(TIMP-2) in human benign and malignant protatic tissue.Prostate.2000,42(1):18-25
11 Gong YI,Xu GM,Huang WD,et al.Expression of matrix metalloproteinases and the tissue inhibitors of metalloproteinases and their local invasiveness and metastasis in Chinese human pancreatic cancer.J Surg Oncol.2000,73(2):95-99
12 Dalberg K,Eriksson E,Enberg U,et al.Gelatinase A,membrane type 1 matrix metalloproteinase,and extracellular matrix metalloproteinase inducer mRNA expression:correlation with invasive growth of breast cancer.World J Surg.2000,24(3):334-340
13 Yoshimoto M,Itoh F,Yamamoto H,et al.Expression of MMP-7(PUMP-1)mRNA in human colorectal cancers.Int J Cancer.1993,54(4):614-618
14 Koshiba T,Hosotani R,Wada M,et al.Involvement of matrix metalloproteinase-2activity invasion and metastasis of pancreatic carcinoma. Cancer. 1998, 82 (4) :642-650
15 Somiari SB, Somiari RI, Heckman CM, et al. Circulating MMP2 and MMP9 in breast cancer — potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int J Cancer. 2006, 119(6):1403-1411
16 Pellikainen JM, Ropponen KM, Kataja VV, et al. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis. Clin Cancer Res.2004, 10(22): 7621-7628.
17 Tang Y, Nakada MT, Kesavan P, et al. Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases.Cancer Res. 2005, 65(8):3193-3199
18 Kurizaki T, Toi M, Tominaga T. Relationship between matrix metalloproteinase expression and tumor angiogenesis in human breast carcinoma. Oncol Rep. 1998, 5(3):673-677
19 Wolk A, Gridley G, Svensson M, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control. 2001, 12(1):13—21.
20 Werner H, LeRoith D. The role of the insulin-like growth factor system in human cancer. Adv Cancer Res. 1996, 68:183-223
21 Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth.Endocr Rev. 2000, 21 (3):215-244
22 Kluge A, Zimmermann R, Munkel B, et al. Insulin-like growth factor I is involved in inflammation linked angiogenic processes after micro-embolisation in porcine heart. Cardiovasc Res. 1995, 29(3): 407-415
23 Youn BS, Min SS, Park KS, et al. The role of adipocytokines in adipocyte-related pathological processes. Drug News Perspect. 2004,17(5):293-298
24 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003,9(15):5699-5704
25 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004, 89(3):1102-11027
26 Manabe Y, Toda S, Miyazaki K, Sugihara H. Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions.J Pathol.2003, 201(2):221-228
27 Brakenhielm E, Veitonmaki N, Cao R, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004, 101(8):2476-2481
28 Leach RE, Romero R, Kim YM, et al. Pre-eclampsia and expression of heparin-binding EGF-like growth factor. Lancet. 2002, 360(9341): 1215-1219
29 Castellucci M, De Matteis R, Meisser A, et al. Leptin modulates extracellular matrix molecules and metalloproteinases: possible implications for trophoblast invasion. Mol Hum Reprod. 2000,6(10):951-958
30 Meisser A, Cameo P, Islami D, et al. Effects of interleukin-6 (IL—6) on cytotrophoblastic cells. Mol Hum Reprod. 1999, 5(11):1055-1058
31 Fujiuchi Y, Nagakawa O, Murakami K, Fuse H, Saiki I. Effect of hepatocyte growth factor on invasion of prostate cancer cell lines.Oncol Rep. 2003, 10(4):1001-1006
32 Lamszus K, Jin L, Fuchs A, et al. Scatter factor stimulates tumor growth and tumor angiogenesis in human breast cancers in the mammary fat pads of nude mice. Lab Invest. 1997, 76(3):339-353
33 Lee PP, Hwang JJ, Murphy G, Ip MM. Functional significance of MMP-9 in tumor necrosis factor-induced proliferation and branching morphogenesis of mammary epithelial cells. Endocrinology. 2000,141(10):3764-3773
34 Leek RD, Landers R, Fox SB, et al. Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma. Br J Cancer. 1998, 77(12):2246-2251
35 Arihiro K, Oda H, Kaneko M, Inai K. Cytokines facilitate chemotactic motility of breast carcinoma cells. Breast Cancer. 2000, 7(3) :221-230
36 Salgado R, Junius S, Benoy I, et al. Circulating interleukin-6 predicts survival in patients with metastatic breast cancer. Int J Cancer. 2003,103(5):642-646
37 Loi S, Milne RL, Friedlander ML, et al. Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev. 2005, 14(7):1686-1691
38 Youn BS, Min SS, Park KS, et al. The role of adipocytokines in adipocyte-related pathological processes. Drug News Perspect. 2004,17(5):293-298
39 Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes.Nature,2001,409(6818):307-312
40 Hou WK,Xian YX,Zhang L,et al.Influence of blood glucose on the expression of glucose trans-porter proteins 1 and 3 in the brain of diabetic rats.Chin Med J(Engl).2007,120(19):1704-1709
41 Guarini 1.Temponi M.Edwards GM,ET AL.In virtro differentiation and antigenic changes in human melanoma cells.Cancer Immunal Immunther,1987,30,262-268
42 Hanemaaier R,Verheijen J H,Mayuire TM,et al.lncreasedgelatinase-A and gelatinase-B activities in mallignant vs benign breast tumors.Int J Cancer.2000,86:204-207
43 Laud K,Gourdou I,Pessemesse L,et al.Identification of leptin receptors in human breast cancer:functional activity in the T47-D breast cancer cell line.Mol Cell Endocrinol.2002,188(1-2):219-226
44 Dieudonne MN,Machinal-Quelin F,Serazin-Leroy V,et al.Leptin mediates a proliferative response in human MCF7 breast cancer cells.Biochem Biophys Res Commun.2002,293(1):622-628
45 Mu H,Ohashi R,Yan S,et al.Adipokine resistin promotes in vitro angiogenesis of human endothelial cells.Cardiovasc Res.2006 Apr 1;70(1):146-157
46 Calabro P,Samudio I,Willerson JT,Yeh ET.Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways.Circulation.2004,110(21):3335-3340
47 Saiki I.Cell adhesion molecules and cancer metastasis.Jpn J Pharmacol,1997,75(3):215-243
48 郝光荣,姚明,朱德生。免疫缺陷动物。见:郝光荣,主编。实验动物学。上海:第二军医大学出版社,第一版,2000,200-202;
49 司徒镇强,吴军正。裸鼠移植瘤动物模型。见:司徒镇强,吴军正,主编。细胞培养。陕西:世界图书出版社,第一版,1996,144-147
50 Maeda k,Okubo K,Shimomura I,et al.CDNA cloning and expression of a novel adipose specific collagen-like factor,apM1(Adipose Most Abundant Oene Transcript 1).Biochem.Biophys Res Commun,1996,221:286 298
51 Chandran M,Phillips SA,Ciaraldi T,et al.idiponectin:more than just another fat cell hormone? Diabetes Care.2003,6(8):2442-2450
52 Tsao TS,Murrey HE,Hug C,et al.Oligomerization state-dependent activation of NF-κB signaling pathway by adipocyte complement-related protein of 30kDa(icrp30).J.Biol.them,2002,277(33):29359-29362
53 Guang W, Jin Wang, Christopher Hug, et al. A family of Acrp30/adiponectin structural and functional paralogs. PNAS. 2004, 101(28):10302-10307
54 Yaraauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423(6941):762-769
55 Kharroubi I, Rasschaert J, Eizirik DL, Cnop M. Expression of adiponectin receptors in pancreatic beta cells. Biochem Biophys Res Commun. 2004, 312 (4):1118-1122
56 Takahata C, Miyoshi Y, Irahara N, et al. Demonstration of adiponectin receptors 1 and 2 mRNA expression in human breast cancer cells. Cancer Lett. 2007, 250(2):229-236
57 Dieudonne MN, Bussiere M, Dos Santos E, et al. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun. 2006, 345(1) :271-279
58 Kang JH, Lee YY, Yu BY, et al. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch Pharm Res. 2005,28(11):1263-1269.
59 Harvie M, Howell A. Energy balance adiposity and breast cancer-energy restriction strategies for breast cancer prevention. Obes Rev. 2006 ,7(1):33-47
60 Chen DC, Chung YF, Yeh YT, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2006, 237(1) :109—114
61 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk, J Clin Endocrinol Metab. 2004 , 89(3):1102-1107
62 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003,9(15):5699-5704
63 Rose DP, Komninou D, Stephenson GD. Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev. 2004 , 5(3):153-165
64 Petridou E, Mantzoros C, Koukoulomatis P,et al. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinoi Metab. 2003 , 88(3):993-997
65 Dal Maso L , Augustin LS, Karalis A, et al. Circulating adiponectin and endometrial cancer risk. J Clin Endocrinoi Metab. 2004 , 89(3):1160-1163
66 IshikawaM, Kitayama J, Kazama S, et al. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005, 11(2 Pt 1):466-472
67 Goktas S, Yilraaz MI, Caglar K, et al. Prostate cancer and adiponectin.Urology. 2005, 65(6):1168-1172
68 Freedland SJ, Sokoll LJ, Platz EA, et al. Association between serum adiponectin, and pathological stage and grade in men undergoing radical prostatectomy. J Urol. 2005, 174(4 Pt 1):1266-1270
69 Wei EK, Giovannucci E, Fuchs CS, et al. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst. 2005, 97(22):1688-1694
70 Petridou E, Mantzoros CS, Dessypris N, et al. Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer. 2006, 94(1) : 156-60.
71 Liotta LA. Tumor invasion and metastases: role of the basement membrane.Am J Pathol. 1984, 117(3) :339-348
72 Hanemaaier R, Verheijen J H, Mayuire TM, et al. Increasedgelatinase-A and gelatinase-B activities in mallignant vs benign breast tumors. Int J Cancer. 2000, 86: 204-207
73 Kaaks R, Toniolo P, Akhmedkhanov A, et al. Serum C-peptide,insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst. 2000 ,92(19):1592-1600
74 Yokata T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.Blood. 2000, 96(5):1723-1732
75 Wang Y, Lam KS, Xu LY, et al. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem. 2005, 280(18): 18341-18347
76 Kang JH, Yu BY, Youn DS. Relationship of serum adiponectin and resist in levels with breast cancer risk. J Korean Med Sci. 2007, 22(1):117-121
1 The World Health Organization MONICA Project(monitoring trends and determinants in cardiovascular disease):a major international collaboration.WHO MONICA Project Principal Investigators.J Clin Epidemiol. 1988, 41(2): 105-114.
2 Kopelman PG. Obesity as a medical problem. Nature. 2000, 404(6778):635-643.
3 Wolk A, Gridley G, Svensson M, et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control. 2001, 12(1):13-21
4 Bergstrom A, Pisani P, Tenet V, Wolk A, Adami HO. Overweight as an avoidable cause of cancer in Europe. Int J Cancer. 2001, 91(3) :421-430
5 Pan SY, Johnson KC, Ugnat AM, et al. Canadian Cancer Registries Epidemiology Research Group. Association of obesity and cancer risk in Canada. Am J Epidemiol. 2004, 159(3):259-268
6 Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity,and mortality from cancer in a prospectively studied cohort of U.S.adults. N Engl J Med. 2003, 348(17):1625-238
7 Werner H, LeRoith D. The role of the insulin-like growth factor system in human cancer. Adv Cancer Res. 1996, 68:183-223
8 Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE. The effects of insulin-like growth factors on tumorigenesis and neoplastic growth.Endocr Rev. 2000
9 Kluge A, Zimmermann R, Munkel B, et al. Insulin-like growth factor I is involved in inflammation linked angiogenic processes after microembolisation in porcine heart. Cardiovasc Res. 1995,29(3):407-415
10 Youn BS, Min SS, Park KS, et al. The role of adipocytokines in adipocyte-related pathological processes. Drug News Perspect. 2004,17(5) :293-298.
11 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003, 9(15):5699-56704
12 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004, 89(3):1102-1107
13 Manabe Y, Toda S, Miyazaki K, Sugihara H. Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions.J Pathol.2003, 201(2):221-228
14 Palmqvist R, Stattin P, Rinaldi S, et al. Plasma insulin, IGF-binding proteins-1 and -2 and risk of colorectal cancer: a prospective study in northern Sweden. Int J Cancer. 2003, 107(1):89-93
15 Giovannucci E. Insulin, insulin-like growth factors and colon cancer: a review of the evidence. J Nutr. 2001, 131(11 Suppl):3109S-3120S
16 Schoen RE, Tangen CM, Kuller LH, et al. Increased blood glucose and insulin, body size, and incident colorectal cancer. J Natl Cancer Inst.1999, 91(13):1147-1154
17 Lawlor DA, Smith GD, Ebrahim S. Hyperinsulinaemia and increased risk of breast cancer: findings from the British Women's Heart and Health Study. Cancer Causes Control. 2004, 15(3) :267-275
18 Kaaks R. Nutrition, hormones, and breast cancer: is insulin the missing link? Cancer Causes Control. 1996, 7(6):605-625
19 Kaaks R, Lukanova A, Kurzer MS. Obesity, endogenous hormones, and endometrial cancer risk: a synthetic review. Cancer Epidemiol Biomarkers Prev. 2002, 11(12):1531-1543
20 Hammarsten J, Hogstedt B. Hyperinsulinaemia: a prospective risk factor for lethal clinical prostate cancer. Eur J Cancer. 2005, 41(18):2887-2895
21 McCarty MF. Chronic activation of AMP-activated kinase as a strategy for slowing aging. Med Hypotheses. 2004, 63(2):334-339
22 Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos D,Adami HO. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. Br J Cancer. 1997, 76(9):1115-1118
23 Bohlke K, Cramer DW, Trichopoulos D, Mantzoros CS. Insulin-like growth factor-I in relation to premenopausal ductal carcinoma in situ of the breast. Epidemiology. 1998, 9(5):570-3.
24 Bruning PF, Van Doom J, Bonfrer JM, Van Noord PA, Korse CM, Linders TC, Hart AA. Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. Int J Cancer.1995, 62(3):266-70.
25 Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B,Rosner B, Speizer FE, Pollak M. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998,351(9113):1393-6.
26 Kaulsay KK, Ng EH, Ji CY, et al. Serum IGF-binding protein-6 and prostate specific antigen in breast cancer. Eur J Endocrinol. 1999,140(2):164-168
27 Ayabe T, Tsutsumi O, Sakai H, et al. Increased circulating levels of insulin-like growth factor-I and decreased circulating levels of insulin-like growth factor binding protein-1 in postmenopausal women with endometrial cancer. Endocr J. 1997, 44(3):419-424
28 Chan JM, Stampfer MJ, Giovannucci E, et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science. 1998,279(5350): 563-566
29 Ma J, Pollak MN, Giovannucci E, et al. Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst. 1999,91(7):620-625
30 Renehan AG, Jones J, Potten CS, et al. Elevated serum insulin-like growth factor (IGF)-II and IGF binding protein-2 in patients with colorectal cancer. Br J Cancer. 2000, 83(10):1344-1350
31 Manousos O, Souglakos J, Bosetti C, et al. IGF-I and IGF—II in relation to colorectal cancer. Int J Cancer. 1999, 83(1):15-17
32 Lee DY, Kim SJ, Lee YC. Serum insulin-like growth factor (IGF)-I and IGF-binding proteins in lung cancer patients. J Korean Med Sci. 1999,14(4):401-404
33 Yu H, Spitz MR, Mistry J, et al. Plasma levels of insulin-like growth factor-I and lung cancer risk: a case-control analysis. J Natl Cancer Inst. 1999, 91(2):151-156
34 Rose DP. Diet, hormones, and cancer. Annu Rev Public Health. 1993, 14:1-17
35 Bulun SE, Mahendroo MS, Simpson ER. Aromatase gene expression in adipose tissue: relationship to breast cancer. J Steroid Biochem Mol Biol. 1994, 49(4-6): 319-26
36 Barbieri RL, Makris A, Randall RW, et al. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab. 1986, 62(5) :904-910
37 Bernstein L, Ross RK. Endogenous hormones and breast cancer risk.Epidemiol Rev. 1993, 15(1) :48-65
38 Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab. 2000, (8):327-332.
39 Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue.Nature. 1994, 372(6505):425-432
40 Miczke A, Pupek-Musialik D. Leptin and obesity. Pol Merkur Lekarski.2000, 8(44): 109-112
41 Nakata M, Yada T, Soejima N, Maruyama I. Leptin promotes aggregation of human platelets via the long form of its receptor. Diabetes. 1999, 48(2):426-429
42 Hu X, Juneja SC, Maihle NJ, Cleary MP. Leptin—a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst. 2002, 94(22):1704-1711
43 Magoffin DA, Weitsman SR, Aagarwal SK, Jakimiuk AJ. Leptin regulation of aromatase activity in adipose stromal cells from regularly cycling women. Ginekol Pol. 1999, 70(1):1-7
44 Cleary MP, Juneja SC, Phillips FC, et al. Leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db) female mice do not develop oncogene-induced mammary tumors. Exp Biol Med (Maywood). 2004,229(2):182-193
45 O' brien SN, Welter BH, Price TM. Presence of leptin in breast cell lines and breast tumors. Biochem Biophys Res Commun. 1999, 259(3): 695-8.
46 Mantzoros CS, Bolhke K, Moschos S, Cramer DW. Leptin in relation to carcinoma in situ of the breast: a study of pre-menopausal cases and controls. Int J Cancer. 1999, 80(4):523-526
47 Petridou E, Papadiamantis Y, Markopoulos C, et al. Leptin and insulin growth factor I in relation to breast cancer (Greece). Cancer Causes Control. 2000, 11 (5):383-388
48 Ozet A, Arpaci F, Yilmaz MI, et al. Effects of tamoxifen on the serum leptin level in patients with breast cancer. Jpn J Clin Oncol. 2001,31(9):424-427.
49. Comings DE, Gade-Andavolu R, Cone LA, et al. A multigene test for the risk of sporadic breast carcinoma. Cancer. 2003, 97(9):2160-2170
50 Liu Z, Uesaka T, Watanabe H, Kato N. High fat diet enhances colonic cell proliferation and carcinogenesis in rats by elevating serum leptin.Int J Oncol. 2001, 19(5):1009-1014
51 Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ,Peppelenbosch MP. Leptin is a growth factor for colonic epithelial cells.Gastroenterology. 2001, 121 (1):79-90
52 Petridou E, Belechri M, Dessypris N, et al. Leptin and body mass index in relation to endometrial cancer risk. Ann Nutr Metab. 2002, 46(3-4) :147-151
53 Yuan SS, Tsai KB, Chung YF, et al. Aberrant expression and possible involvement of the leptin receptor in endometrial cancer. Gynecol Oncol.2004, 92(3):769-775
54 Chan TF, Su JH, Chung YF, et al. Decreased serum leptin levels in women with uterine leiomyomas. Acta Obstet Gynecol Scand. 2003, 82(2): 173— 176
55 Huang KC, Chuang LM, Chen CY, et al. Serum leptin and leptin receptor isoforms in omental adipose tissue of nondiabetic women undergoing gy necologic surgery for benign disease. J Formos Med Assoc, 2000, 99(11):839-843.
56 Remsberg KE, Talbe tt EO, Zberowski JV, et al. Evidence for competing efects of body mass, hyperinsulinemia, insulin resistance, an dandrogens on leptin levels among lean, overweight, and obe se women with polycystic ovary syndrome. Fertil Steril, 2002, 78(3): 479-486
57 Stattin P, Soderbe rg S, Hallman s G, et al. Leptin is associated with increased prostate can cer risk: a nested case-referent study. J Clin Endocrinol Metab, 2001, 86(3): 1341—1345.
58 Chang S, Humting SD, Contois JH, et al. Leptin and prostate cancer. Prostate, 2001, 46(1): 62-67.
59 Nakao T, Hino M , Yamane T, et al. Expression of the leptin receptor in human leukaemic blast cells. Br J Haematol, 1998, 102(3): 740-745.
60 Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita M. Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem (Tokyo). 1996, 120(4):803-12.
61 Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem. 1996, 271(18):10697-10703.
62 Scherer PE, Williams S, FoglianoM, et al. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995,270(45):26746-26749.
63 Pineiro R, Iglesias MJ, Gallego R, et al. Adiponectin is synthesized and secreted by human and murine cardiomyocytes. FEBS Lett. 2005,579(23):5163-5169.
64 Chen J, Tan B, Karteris E, et al. Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines. Diabetologia. 2006, 49(6):1292-1302.
65 Takahashi M, AritaY, YamagataK, et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord.2000, 24(7) :861-868.
66 Kissebah AH, Sonnenberg GE, Myklebust J, et al. Quantitative trait locion chromosomes 3 and 17 influence phenotypes of the metabolic syndrome.Proc Natl Acad Sci U S A. 2000, 97(26):14478-14483.
67 Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.Blood. 2000, 96(5): 1723-1732.
68 Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin.Circulation. 1999, 100(25):2473-2476.
69 Ouchi N, Kihara S, Arita Y, et al.. Adipocyte-derived plasma protein,adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation.2001, 103(8):1057-1063.
70 Wong GW, Wang J, Hug C, et al. A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci U S A. 2004,101 (28):10302-10307.
71 Tsao TS, Murrey HE, Hug C, et al. Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30). J Biol Chem. 2002,277(33): 29359-29362.
72 Peake PW, Kriketos AD, Campbell LV, et al. The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals. Eur J Endocrinol. 2005, 153(3):409-417.
73 Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005, 26(3):439-451
74 Fruebis J, Tsao TS, Javorschi S, et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A. 2001, 98(4):2005-2010
75 Waki H, Yamauchi T, Kamon J, et al. Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endocrinology. 2005, 146(2):790-796.
76 Goldstein BJ, Scalia R. Adiponectin: A novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab. 2004,89(6):2563-2568.
77 Tsao TS, Tomas E, Murrey HE, et al. Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. J Biol Chem.2003, 278(50):50810-50817.
78 Tomas E, Tsao TS, Saha AK, et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci U S A. 2002, 99(25):16309-16313.
79 Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med. 2001, 7(8) :947-953.
80 Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. J Biol Chem. 2003, 278(11): 9073-9085.
81 Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem. 2004, 279(13):12152-12162.
82 Fisher FF, Trujillo ME, Hanif W, et al. Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia. 2005,48(6):1084-1087.
83 Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423(6941):762-769.
84 Kharroubi I, Rasschaert J, Eizirik DL, Cnop M. Expression of adiponectin receptors in pancreatic beta cells. Biochem Biophys Res Commun. 2003, 312(4):1118-1122.
85 Miyazaki T, Bub JD, Uzuki M, Iwamoto Y. Adiponectin activates c-Jun NH2-terminal kinase and inhibits signal transducer and activator of transcription 3. Biochem Biophys Res Commun. 2005, 333(1) :79-87.
86 Tsuchida A, Yamauchi T, Ito Y, et al. Insulin/Foxol pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity.J Biol Chem. 2004, 279(29):30817-30822.
87 Inukai K, Nakashima Y, Watanabe M, et al. Regulation of adiponectin receptor gene expression in diabetic mice. Am J Physiol Endocrinol Metab.2005, 288(5):E876-82.
88 Oana F, Takeda H, Hayakawa K, Matsuzawa A, et al. Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin. Metabolism. 2005, 54(8):995-1001.
89 Tsuchida A, Yamauchi T, Takekawa S, et al. Peroxisome proliferator-activated receptor (PPAR)alpha activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue:comparison of activation of PPARalpha, PPARgamma, and their combination.Diabetes. 2005, 54(12):3358-3370.
90 Kaltenbach S, Staiger H, Weisser M, et al. Adiponectin receptor gene expression in human skeletal muscle cells is not regulated by fibrates and thiazolidinediones. Int J Obes (Lond). 2005, 29(7):760-765.
91 Adachi Y, Takeuchi T, Sonobe H, Ohtsuki Y. An adiponectin receptor,T-cadherin, was selectively expressed in intratumoral capillary endothelial cells in hepatocellular carcinoma: possible cross talk between T-cadherin and FGF-2 pathways. Virchows Arch. 2006, 448(3):311-318.
92 Dal Maso L, Augustin LS, Karalis A, et al. Circulating adiponectin and endometrial cancer risk. J Clin Endocrinol Metab. 2004,89(3): 1160-1163.
93 Petridou E, Mantzoros C, Dessypris N, et al. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinol Metab. 2003, 88(3):993-997.
94 Alvarez BV, Johnson DE, Sowah D, et al. Carbonic anhydrase inhibition prevents and reverts cardiomyocyte hypertrophy. J Physiol. 2007, 579(Pt 1): 127-145.
95 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004, 89(3):1102-1107.
96 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003,9(15):5699-5704.
97 Chen DC, Chung YF, Yeh YT, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2006, 237(1): 09-14.
98 Wei EK, Giovannucci E, Fuchs CS, et al. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study, J Natl Cancer Inst. 2005, 97(22) :1688-94.
99 Otake S, Takeda H, Suzuki Y, et al. Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance. Clin Cancer Res. 2005, 11(10):3642-6.
100 Ishikawa M, Kitayama J, Kazama S, et al. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005, 11(2 Pt 1):466-72.
101 Freedland SJ, Sokoll LJ, Platz EA, et al. Association between serum adiponectin, and pathological stage and grade in men undergoing radical prostatectomy. J Urol. 2005, 174(4 Pt 1):1266-70.
102 Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S, Bedir S. Prostate cancer and adiponectin. Urology. 2005, 65(6):1168-72.
103 Petridou E, Mantzoros CS, Dessypris N, et al. Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer. 2006, 94(1):156-60.
104 Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.Blood. 2000, 96(5): 1723-32.
105 Kang JH, Lee YY, Yu BY, et al. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch Pharm Res. 2005,28(11): 1263-9.
106 Dieudonne MN, Bussiere M, Dos Santos E, et al. Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. Biochem Biophys Res Commun. 2006, 345(1):271-9.
107 Bub JD, Miyazaki T, Iwamoto Y. Adiponectin as a growth inhibitor in prostate cancer cells. Biochem Biophys Res Commun. 2006, 340(4):1158-66.
108 Brakenhielm E, Veitonmaki N, et al. Adiponectin-induced antiangio-genesis and antitumor activity involve caspase-mediated endothelial cell apoptosis. Proc Natl Acad Sci U S A. 2004, 101(8): 2476-81.
109 Manabe Y, Toda S, Miyazaki K, Sugihara H. Mature adipocytes, but not preadipocytes, promote the growth of breast carcinoma cells in collagen gel matrix culture through cancer-stromal cell interactions. J Pathol.2003, 201(2):221-228
1 Maeda k,Okubo K,Shimomura I,et al.CDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (Adipose Most Abundant Gene Transcript 1). Biochem. Biophys Res Commun, 1996,221:286-298.
2 Chandran M, Phillips SA, Ciaraldi T, et al. Adiponectin: more than just another fat cell hormone? Diabetes Care. 2003, 6(8): 2442-50.
3 Tsao TS, Murrey HE, Hug C, et al. Oligomerizat'ion state-dependent activation of NF-κ B signaling pathway by adipocyte complement-related protein of 30kDa(Acrp30). J.Biol. Chem, 2002, 277(33): 29359-29362.
4 GuangW, Jin Wang, Christopher Hug, et al. A family of Acrp30/adiponectin structural and functional paralogs. PNAS. 2004,101 (28): 10302-10307.
5 Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003, 423(6941) :762-9.
6 Kharroubi I, Rasschaert J, Eizirik DL, Cnop M. Expression of adiponectin receptors in pancreatic beta cells. Biochem Biophys Res Commun. 2004 ,312 (4): 1118-22.
7 Harvie M, Howell A. Energy balance adiposity and breast cancer-energy restriction strategies for breast cancer prevention. Obes Rev. 2006 ,7(1):33-47.
8 Chen DC, Chung YF, Yeh YT, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2005 Jul 11.
9 Mantzoros C, Petridou E, Dessypris N, et al. Adiponectin and breast cancer risk. J Clin Endocrinol Metab. 2004 , 89(3):1102-7.
10 Miyoshi Y, Funahashi T, Kihara S, et al. Association of serum adiponectin levels with breast cancer risk. Clin Cancer Res. 2003,9(15):5699-704.
11 Kang JH, Lee YY, Yu BY, et al. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch Pharm Res. 2005,28(11):1263-9.
12 Rose DP, Komninou D, Stephenson GD. Obesity, adipocytokines, and insulin resistance in breast cancer. Obes Rev. 2004 , 5(3):153-65.
13 Petridou E, Mantzoros C, Koukoulomatis P, et al. Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. J Clin Endocrinol Metab. 2003 , 88(3):993-7.
14 Dal Maso L , Augustin LS, Karalis A, et al. Circulating adiponectin and endometrial cancer risk. J Clin Endocrinol Metab. 2004 ,89(3): 1160-3.
15 Chen HS, Chan TF, Chung YF, et al. Aberrant serum adiponectin levels in women with uterine leiomyomas. Gynecol Obstet Invest. 2004,58(3):160-3
16 Ishikawa M, Kitayama J, Kazama S, et al. Plasma adiponectin and gastric cancer. Clin Cancer Res. 2005, 11(2 Pt 1):466-72.
17 Goktas S, Yilmaz MI, Caglar K, et al. Prostate cancer and adiponectin.Urology. 2005, 65(6):1168-72.
18 Freedland SJ, Sokoll LJ, Platz EA, et al. Association between serum adiponectin, and pathological stage and grade in men undergoing radical prostatectomy. J Urol. 2005, 174(4 Pt 1):1266-70.
19 Wei EK, Giovannucci E, Fuchs CS, et al. Low plasma adiponectin levels and risk of colorectal cancer in men: a prospective study. J Natl Cancer Inst. 2005, 97(22):1688-94.
20 Otake S, Takeda H, Suzuki Y, et al. Association of visceral fat accumulation and plasma adiponectin with colorectal adenoma: evidence for participation of insulin resistance. Clin Cancer Res.2005,11 (10): 3642-6.
21 Petridou E, Mantzoros CS, Dessypris N, et al. Adiponectin in relation to childhood myeloblastic leukaemia. Br J Cancer. 2006, 94(1) :156-60.
22 Kaaks R, Toniolo P, Akhmedkhanov A, et al. Serum C-peptide,insulin-like growth factor (IGF)-I, IGF-binding proteins, and colorectal cancer risk in women. J Natl Cancer Inst. 2000 ,92(19): 1592-600.
23 Yokata T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myeiomonocytic progenitors and the functions of macrophages. Blood. 2000, 96(5):1723-32.
24 Wang Y, Lam KS, Xu LY, et al. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem. 2005, 280(18):18341-7.
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