B-cell lymphoma 6 protein stimulates oncogenicity of human breast cancer cells

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• 作者：Qiang Wu (1)
  Xue Liu (1)
  Hong Yan (1)
  Yin-huan He (1)
  Shan Ye (1)
  Xing-wang Cheng (2)
  Gui-lu Zhu (1)
  Wen-yong Wu (3)
  Xiao-nan Wang (1)
  Xiang-jun Kong (4)
  Xiao-chun Xu (5)
  Peter E Lobie (6)
  Tao Zhu (4)
  Zheng-sheng Wu (1)
  
  1. Department of Pathology ; Anhui Medical University ; Hefei ; Anhui ; China
  2. Department of Emergency Surgery ; The First Affiliated Hospital ; Bengbu Medical University ; Anhui ; Bengbu ; China
  3. Department of General Surgery ; The First Affiliated Hospital ; Anhui Medical University ; Hefei ; Anhui ; China
  4. School of Life Science ; Chinese University of Science and Technology ; Hefei ; Anhui ; China
  5. Department of Clinical Cancer Prevention ; The University of Texas MD Anderson Cancer Center ; Houston ; Texas ; USA
  6. Cancer Science Institute of Singapore and Department of Pharmacology ; National University of Singapore ; Singapore ; Singapore
  
• 关键词：Breast cancer ; BCL6 ; microRNA
• 刊名：BMC Cancer
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：1,186 KB
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  36. The pre-publication history for this paper can be accessed here: http://www.biomedcentral.com/1471-2407/14/418/prepub
  
• 刊物主题：Cancer Research; Oncology; Stem Cells; Animal Models; Internal Medicine;
• 出版者：BioMed Central
• ISSN：1471-2407

文摘

Background B-cell lymphoma 6 (BCL6) protein, an evolutionarily conserved zinc finger transcription factor, showed to be highly expressed in various human cancers in addition to malignancies in the lymphoid system. This study investigated the role of BCL6 expression in breast cancer and its clinical significance in breast cancer patients. Methods Expression of BCL6 protein was assessed using in situ hybridization and immunohistochemistry in 127 breast cancer patients and 50 patients with breast benign disease as well as in breast cell lines. Expression of BCL6 was restored or knocked down in two breast cancer cell lines (MCF-7 and T47D) using BCL6 cDNA and siRNA, respectively. The phenotypic change of these breast cancer cell lines was assessed using cell viability MTT, Transwell invasion, colony formation, and flow cytometry assays and in a xenograft mice model. Luciferase reporter gene, immunoblot, and qRT-PCR were used to investigate the molecular events after manipulated BCL6 expression in breast cancer cells. Results BCL6 protein was highly expressed in breast cancer cell lines and tissue specimens and expression of BCL6 protein was associated with disease progression and poor survival of breast cancer patients. In vitro, the forced expression of BCL6 results in increased proliferation, anchorage-independent growth, migration, invasion and survival of breast cancer cell lines, whereas knockdown of BCL6 expression reduced these oncogenic properties of breast cancer cells. Moreover, forced expression of BCL6 increased tumor growth and invasiveness in a nude mouse xenograft model. At the gene level, BCL6 was a target gene of miR-339-5p. Expression of BCL6 induced expression of CXCR4 and cyclinD1 proteins. Conclusions The current study demonstrated the oncogenic property of BCL6 in breast cancer and further study could target BCL6 as a novel potential therapeutic strategy for breast cancer.