Estrogen receptor α mediates proliferation of breast cancer MCF-7 cells via a p21/PCNA/E2F1-dependent pathway

Xing-Hua Liao; Da-Lin Lu; Nan Wang; Long-Yue Liu; Yue Wang; Yan-Qi Li; Ting-Bao Yan; Xue-Guang Sun; Peng Hu; Tong-Cun Zhang

doi:10.1111/febs.12658

Estrogen receptor α mediates proliferation of breast cancer MCF-7 cells via a p21/PCNA/E2F1-dependent pathway

FEBS J. 2014 Feb;281(3):927-42. doi: 10.1111/febs.12658. Epub 2014 Jan 2.

Authors

Xing-Hua Liao¹, Da-Lin Lu, Nan Wang, Long-Yue Liu, Yue Wang, Yan-Qi Li, Ting-Bao Yan, Xue-Guang Sun, Peng Hu, Tong-Cun Zhang

Affiliation

¹ 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.

PMID: 24283290
DOI: 10.1111/febs.12658

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.

Keywords: MCF-7 cell proliferation; PCNA; estrogen receptor α (ERα); miR-17; p21.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Cycle
Cell Proliferation
Cyclin-Dependent Kinase Inhibitor p21 / antagonists & inhibitors
Cyclin-Dependent Kinase Inhibitor p21 / genetics
Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
E2F1 Transcription Factor / genetics
E2F1 Transcription Factor / metabolism*
Estradiol / metabolism
Estrogen Receptor alpha / agonists
Estrogen Receptor alpha / antagonists & inhibitors
Estrogen Receptor alpha / genetics
Estrogen Receptor alpha / metabolism*
Female
Gene Expression Regulation, Neoplastic
Gene Silencing
Humans
Ki-67 Antigen / biosynthesis
Ki-67 Antigen / genetics
Ki-67 Antigen / metabolism
MCF-7 Cells
MicroRNAs / biosynthesis
MicroRNAs / metabolism
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism*
Proliferating Cell Nuclear Antigen / genetics
Proliferating Cell Nuclear Antigen / metabolism*
Recombinant Proteins / biosynthesis
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism
Response Elements
Signal Transduction*
Tumor Suppressor Protein p53 / antagonists & inhibitors
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism

Substances

CDKN1A protein, human
Cyclin-Dependent Kinase Inhibitor p21
E2F1 Transcription Factor
E2F1 protein, human
ESR1 protein, human
Estrogen Receptor alpha
Ki-67 Antigen
MIRN17 microRNA, human
MicroRNAs
Neoplasm Proteins
Proliferating Cell Nuclear Antigen
Recombinant Proteins
TP53 protein, human
Tumor Suppressor Protein p53
Estradiol