LIM结构域结合蛋白1在脑胶质瘤患者中的表达研究
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摘要
目的观察LIM结构域结合蛋白1(LIM-domain-binding 1,Ldb1)在脑胶质瘤患者中的表达。方法采用Real-time PCR方法检测46例脑胶质瘤手术患者脑组织、18例正常对照和16例良性脑肿瘤对照脑组织标本中Ldb1 mRNA的表达水平;采用免疫组化En Vision二步法观察Ldb1在高级别胶质瘤中的蛋白表达定位。结果脑胶质瘤患者脑组织Ldb1的mRNA表达高于正常对照组和良性脑肿瘤对照组。Ldb1在不同分级的胶质瘤中表达并不相同,在III、IV级中的相对表达量明显高于Ⅰ、Ⅱ级(P<0.001)。在高级别胶质瘤中,Ldb1蛋白主要表达在肿瘤细胞核和胞浆内。结论脑胶质瘤患者肿瘤组织中Ldb1表达增高,可能参与了胶质瘤的发生、发展过程。
Objective To investigate the expression of Ldb1 in human gliomas and normal brain tissues and evaluate its clinical significance. Methods The level of LIM-domain-binding 1( Ldb1) in brain specimens collected from 46 patients with gliomas,18 normal controls and 16 benign brain tumors was measured by quantitative real-time PCR. En Vision Immunohistochemistry technique was also applied to detect the protein expression of Ldb1 in formalin-fixed paraffin embedded samples of high-grade gliomas. Results Ldb1 expression in glioma patients was statistically higher than that in the controls. Compared with that in low-grade gliomas,Ldb1 mRNA levels in high-grade gliomas were significantly increased( P < 0. 001). Ldb1 protein was localized in nucleus and cytoplasmin human high-grade glioma cells. Conclusion The expression of Ldb1 is elevated in glioma cells. It may be related to the occurrence and development of glioma.
Objective To investigate the expression of Ldb1 in human gliomas and normal brain tissues and evaluate its clinical significance. Methods The level of LIM-domain-binding 1( Ldb1) in brain specimens collected from 46 patients with gliomas,18 normal controls and 16 benign brain tumors was measured by quantitative real-time PCR. En Vision Immunohistochemistry technique was also applied to detect the protein expression of Ldb1 in formalin-fixed paraffin embedded samples of high-grade gliomas. Results Ldb1 expression in glioma patients was statistically higher than that in the controls. Compared with that in low-grade gliomas,Ldb1 mRNA levels in high-grade gliomas were significantly increased( P < 0. 001). Ldb1 protein was localized in nucleus and cytoplasmin human high-grade glioma cells. Conclusion The expression of Ldb1 is elevated in glioma cells. It may be related to the occurrence and development of glioma.
引文
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[3]Bach I,Carriere C,Ostendorff H P,et al.A family of LIM domainassociated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins.Genes Dev,1997,11(11):1370-1380.
[4]Agulnick A D,Taira M,Breen J J,et al.Interactions of the LIMdomain-binding factor Ldb1 with LIM homeodomain proteins.Nature,1996,384(6606):270-272.
[5]Breen J J,Agulnick A D,Westphal H,et al.Interactions between LIM domains and the LIM domain-binding protein Ldb1.J Biol Chem,1998,273(8):4712-4717.
[6]Matthews J M,Visvader J E.LIM-domain-binding protein 1:a multifunctional cofactor that interacts with diverse proteins.EMBO Rep,2003,4(12):1132-1137.
[7]Mukhopadhyay M,Teufel A,Yamashita T,et al.Functional ablation of the mouse Ldb1 gene results in severe patterning defects during gastrulation.Development,2003,130(3):495-505.
[8]Teufel A,Maass T,Strand S,et al.Liver-specific Ldb1 deletion results in enhanced liver cancer development.J Hepatol,2010,53(6):1078-1084.
[9]Mizunuma H,Miyazawa J,Sanada K,et al.The LIM-only protein,LMO4,and the LIM domain-binding protein,LDB1,expression in squamous cell carcinomas of the oral cavity.Br J Cancer,2003,88(10):1543-1548.
[10]Salmans M L,Yu Z,Watanabe K,et al.The co-factor of LIM domains(CLIM/LDB/NLI)maintains basal mammary epithelial stem cells and promotes breast tumorigenesis.PLo S Genet,2014,10(7):e1004520.
[11]董成亚,李昊文,刘丽,等.脑胶质瘤患者LMO-1和LMO-4基因表达水平的改变及其意义.标记免疫分析与临床,2014,21(5):568-570.
[12]赵伟东,陈誉华.LIM域结合蛋白研究进展.生命科学,2002,14(1):43-46.
[13]Asprer J S,Lee B,Wu C S,et al.LMO4 functions as a coactivator of neurogenin 2 in the developing cortex.Development,2011,138(13):2823-2832.
[14]Zhao Y,Kwan K M,Mailloux C M,et al.LIM-homeodomain proteins Lhx1 and Lhx5,and their cofactor Ldb1,control Purkinje cell differentiation in the developing cerebellum.Proc Natl Acad Sci U S A,2007,104(32):13182-13186.
[15]Johnsen S A,Gungor C,Prenzel T,et al.Regulation of estrogendependent transcription by the LIM cofactors CLIM and RLIM in breast cancer.Cancer Res,2009,69(1):128-136.
[2]Cohen A L,Colman H.Glioma biology and molecular markers.Cancer Treat Res,2015,163:15-30.
[3]Bach I,Carriere C,Ostendorff H P,et al.A family of LIM domainassociated cofactors confer transcriptional synergism between LIM and Otx homeodomain proteins.Genes Dev,1997,11(11):1370-1380.
[4]Agulnick A D,Taira M,Breen J J,et al.Interactions of the LIMdomain-binding factor Ldb1 with LIM homeodomain proteins.Nature,1996,384(6606):270-272.
[5]Breen J J,Agulnick A D,Westphal H,et al.Interactions between LIM domains and the LIM domain-binding protein Ldb1.J Biol Chem,1998,273(8):4712-4717.
[6]Matthews J M,Visvader J E.LIM-domain-binding protein 1:a multifunctional cofactor that interacts with diverse proteins.EMBO Rep,2003,4(12):1132-1137.
[7]Mukhopadhyay M,Teufel A,Yamashita T,et al.Functional ablation of the mouse Ldb1 gene results in severe patterning defects during gastrulation.Development,2003,130(3):495-505.
[8]Teufel A,Maass T,Strand S,et al.Liver-specific Ldb1 deletion results in enhanced liver cancer development.J Hepatol,2010,53(6):1078-1084.
[9]Mizunuma H,Miyazawa J,Sanada K,et al.The LIM-only protein,LMO4,and the LIM domain-binding protein,LDB1,expression in squamous cell carcinomas of the oral cavity.Br J Cancer,2003,88(10):1543-1548.
[10]Salmans M L,Yu Z,Watanabe K,et al.The co-factor of LIM domains(CLIM/LDB/NLI)maintains basal mammary epithelial stem cells and promotes breast tumorigenesis.PLo S Genet,2014,10(7):e1004520.
[11]董成亚,李昊文,刘丽,等.脑胶质瘤患者LMO-1和LMO-4基因表达水平的改变及其意义.标记免疫分析与临床,2014,21(5):568-570.
[12]赵伟东,陈誉华.LIM域结合蛋白研究进展.生命科学,2002,14(1):43-46.
[13]Asprer J S,Lee B,Wu C S,et al.LMO4 functions as a coactivator of neurogenin 2 in the developing cortex.Development,2011,138(13):2823-2832.
[14]Zhao Y,Kwan K M,Mailloux C M,et al.LIM-homeodomain proteins Lhx1 and Lhx5,and their cofactor Ldb1,control Purkinje cell differentiation in the developing cerebellum.Proc Natl Acad Sci U S A,2007,104(32):13182-13186.
[15]Johnsen S A,Gungor C,Prenzel T,et al.Regulation of estrogendependent transcription by the LIM cofactors CLIM and RLIM in breast cancer.Cancer Res,2009,69(1):128-136.