+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

The SMRT coregulator enhances growth of estrogen receptor-α-positive breast cancer cells by promotion of cell cycle progression and inhibition of apoptosis



The SMRT coregulator enhances growth of estrogen receptor-α-positive breast cancer cells by promotion of cell cycle progression and inhibition of apoptosis



Endocrinology 155(9): 3251-3261



The SMRT coregulator functions as a dual coactivator and corepressor for estrogen receptor-α (ERα) in a gene-specific manner, and in several studies its elevated expression correlates with poor outcome for breast cancer patients. A specific role of SMRT in breast cancer progression has not been elucidated, but SMRT knock-down limits estradiol-dependent growth of MCF-7 breast cancer cells. In this study, small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) approaches were used to determine the effects of SMRT depletion on growth of ERα-positive MCF-7 and ZR-75-1 breast cancer cells, as well as the ERα-negative MDA-MB-231 breast cancer line. Depletion of SMRT inhibited growth of ERα-positive cells grown in monolayer but had no effect on growth of the ERα-negative cells. Reduced SMRT levels also negatively impacted the anchorage-independent growth of MCF-7 cells as assessed by soft agar colony formation assays. The observed growth inhibitions were due to a loss of estradiol-induced progression through the G1/S transition of the cell cycle and increased apoptosis in SMRT-depleted compared with control cells. Gene expression analyses indicated that SMRT inhibits apoptosis by a coordinated regulation of genes involved in apoptosis. Functioning as a dual coactivator for anti-apoptotic genes and corepressor for pro-apoptotic genes, SMRT can limit apoptosis. Together these data indicate that SMRT promotes breast cancer progression through multiple pathways leading to increased proliferation and decreased apoptosis.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 056216692

Download citation: RISBibTeXText

PMID: 24971610

DOI: 10.1210/en.2014-1002


Related references

Cell cycle progression stimulated by tamoxifen-bound estrogen receptor-alpha and promoter-specific effects in breast cancer cells deficient in N-CoR and SMRT. Molecular Endocrinology 19(6): 1543-1554, 2005

Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells. Journal of Nutritional Biochemistry 21(9): 856-864, 2010

Estrogen-mediated upregulation of Noxa is associated with cell cycle progression in estrogen receptor-positive breast cancer cells. Plos one 6(12): E29466, 2011

Antineoplastic effects of α-santalol on estrogen receptor-positive and estrogen receptor-negative breast cancer cells through cell cycle arrest at G2/M phase and induction of apoptosis. Plos one 8(2): E56982, 2013

Differential control of growth, cell cycle progression, and gene expression in human estrogen receptor positive MCF-7 breast cancer cells by extracts derived from polysaccharopeptide I'm-Yunity and Danshen and their combination. International Journal of Oncology 29(5): 1215-1222, 2006

Estrogen receptor-negative breast cancer cells transfected with estrogen receptor exhibit decreased tumour progression and sensitivity to growth inhibition by estrogen. Chinese Medical Sciences Journal 12(1): 11-14, 1997

Coenzyme Q 0 Enhances Ultraviolet B-Induced Apoptosis in Human Estrogen Receptor-Positive Breast (MCF-7) Cancer Cells. Integrative Cancer Therapies 16(3): 385-396, 2017

Inhibition of growth of estrogen receptor positive and estrogen receptor negative breast cancer cells in culture by AA-etherA, a stable 2-5A derivative. Oncogene 12(4): 827-837, 1996

Inhibition of Nicotinamide Phosphoribosyltransferase Induces Apoptosis in Estrogen Receptor-Positive MCF-7 Breast Cancer Cells. Journal of Breast Cancer 20(1): 20-26, 2017

Autophagy Inhibition with Monensin Enhances Cell Cycle Arrest and Apoptosis Induced by mTOR or Epidermal Growth Factor Receptor Inhibitors in Lung Cancer Cells. Tuberculosis and Respiratory Diseases 75(1): 9, 2013

Epidermal growth factor-induced nuclear factor kB activation: a major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America 97(15): 42-7, 2000

The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 enhances the antitumor effect of the antiestrogen ICI 182,780 in estrogen-receptor-positive breast cancer cells. Breast Cancer Research & Treatment 76(Suppl. 1): S71, 2002

Epidermal growth factor-induced nuclear factor kappa B activation: A major pathway of cell-cycle progression in estrogen-receptor negative breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America 97(15): 8542-8547, 2000

Smad4 Inhibits Tumor Growth by Inducing Apoptosis in Estrogen Receptor--positive Breast Cancer Cells. Journal of biological chemistry22 280(29): 27022-27028, 2005

Growth inhibition of estrogen receptor-positive and aromatase-positive human breast cancer cells in monolayer and spheroid cultures by letrozole, anastrozole, and tamoxifen. Journal of Steroid Biochemistry and Molecular Biology 97(4): 360-368, 2005