title: Estrogen receptor α mediates proliferation of breast cancer MCF-7 cells via a p21/PCNA/E2F1-dependent pathway.
abstract: High expression of estrogen receptor α (ERα) is associated with a poor prognosis that correlates closely with cellular proliferation in breast cancer. However, the exact molecular mechanism by which ERα controls breast cancer cell proliferation is not clear. Here we report that ERα regulates the cell cycle by suppressing p53/p21 and up-regulating proliferating cell nuclear antigen (PCNA) and proliferation-related Ki-67 antigen (Ki-67) to promote proliferation of MCF-7 cells. In addition, 17-β-estradiol (E2) enhances ERα-induced proliferation of MCF-7 cells by stimulating expression of PCNA and Ki-67. Knockdown of ERα significantly affects PCNA/Ki-67 and p53/p21 expression. Furthermore, ERα inhibits the transcriptional activity of p53/p21 in an estrogen response element-dependent manner. More importantly, we provide new evidence that ERα mediates proliferation of MCF-7 cells by up-regulating miR-17 to silence the expression of p21. Thus, these data provide new insights into the underlying effect of ERα on breast cancer proliferation.
authors.affiliation: Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, China; Institute of Biology and Medicine, Wuhan University of Science and Technology, China.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Liao
authors.forename: Da-Lin
authors.initials: DL
authors.lastname: Lu
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Long-Yue
authors.initials: LY
authors.lastname: Liu
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan-Qi
authors.initials: YQ
authors.lastname: Li
authors.forename: Ting-Bao
authors.initials: TB
authors.lastname: Yan
authors.forename: Xue-Guang
authors.initials: XG
authors.lastname: Sun
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.forename: Tong-Cun
authors.initials: TC
authors.lastname: Zhang
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004958:Estradiol
keywords: MCF-7 cell proliferation; PCNA; estrogen receptor α (ERα); miR-17; p21