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

Endocrinology | Sep 25, 2014

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.

Pubmed ID: 24971610 RIS Download

Mesh terms: Apoptosis | Breast Neoplasms | Cell Cycle | Cell Proliferation | Estrogen Receptor alpha | Female | Humans | MCF-7 Cells | Nuclear Receptor Co-Repressor 2

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Associated grants

  • Agency: NIAID NIH HHS, Id: P30AI036211
  • Agency: NICHD NIH HHS, Id: T32 HD007165
  • Agency: NCRR NIH HHS, Id: S10RR024574
  • Agency: NCI NIH HHS, Id: P30CA125123
  • Agency: NIDDK NIH HHS, Id: R01 DK053002
  • Agency: NCI NIH HHS, Id: P30 CA125123
  • Agency: NIAID NIH HHS, Id: P30 AI036211
  • Agency: NIDDK NIH HHS, Id: DK53002
  • Agency: NCRR NIH HHS, Id: S10 RR024574
  • Agency: NICHD NIH HHS, Id: T32HD07165

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