E2F7 overexpression leads to tamoxifen resistance in breast cancer cells by competing with E2F1 at miR-15a/16 promoter

• DOI: 10.18632/oncotarget.5128
• Publication Date: 2015-09-29T21:54:23Z
• Authors: Junjun Chu; Yinghua Zhu; Yujie Liu; Lijuan Sun; Xiaobin Lv; Yanqin Wu; Pengnan Hu; Fengxi Su; Chang Gong; Erwei Song; Bodu Liu; Qiang Liu
• Keywords: 0301 basic medicine; Chromatin Immunoprecipitation; Antineoplastic Agents, Hormonal; Blotting, Western; Cell Cycle; Apoptosis; Breast Neoplasms; Middle Aged; Prognosis; 3. Good health; Gene Expression Regulation, Neoplastic; Immunoenzyme Techniques; MicroRNAs; 03 medical and health sciences; E2F7 Transcription Factor; Drug Resistance, Neoplasm; Humans; Female; RNA, Messenger; Neoplasm Recurrence, Local; Promoter Regions, Genetic; E2F1 Transcription Factor; Cell Proliferation

// Junjun Chu 1, 2, 3 , Yinghua Zhu 2 Yujie Liu Lijuan Sun Xiaobin Lv Yanqin Wu Pengnan Hu Fengxi Su Chang Gong Erwei Song Bodu Qiang 1 Breast Tumor Center, Yat-sen Memorial Hospital, University, Guangzhou 510120, China Key Laboratory of Malignant Gene Regulation and Target Therapy Guangdong Higher Education Institutes, Engineering Ministry Education, State Biocontrol, School Life Sciences, 510275, Correspondence to: Liu, e-mail: [e-mail] [e-mail] Keywords: breast cancer, tamoxifen resistance, E2F7, miR-15a/16, prognostic marker Received: March 18, 2015 Accepted: August 31, Published: September 12, ABSTRACT About 50–70% cancers are estrogen receptor α (ERα) positive most them sensitive to endocrine therapy including tamoxifen. However, one third these patients will eventually develop resistance relapse. We found that the expression miR-15a miR-16 were significantly decreased in resistant ER cancer cell lines. Exogenous miR-15a/16 mimics re-sensitized cells by inhibiting Cyclin E1 B lymphoma-2 (Bcl-2) induce growth arrest apoptosis respectively. Further, we identified a repressive member E2F family, was responsible for suppression cluster competing with E2F1 binding site at promoter their host gene DLEU2. Moreover, high E2F7 is correlated risk relapse poor prognosis receiving treatment. Together, our results suggest overexpression represses then increases Bcl-2 result resistance. may be valuable therapeutic target cancer.