Involvement of Nuclear Receptor Co-repressors in the Development of Human Breast Cancers
Annual rept. 1 Sep 1998-31 Aug 1999
MASSACHUSETTS UNIV MEDICAL CENTER WORCESTER
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All-trans retinoic acid RA inhibits proliferation of breast cancer cells, mediated by its nuclear receptor RAR. In the absence of RA, the RAR represses basal transcription through direct interaction with SMRT silencing mediator for retinoid and thyroid receptors or N-CoR nuclear receptor corepressor. In this project, we characterized receptor interaction and transcriptional repression mediated by SMRT and N-CoR. We investigated the expression and regulation of SMRT in breast cancer cells. We identified two nuclear receptor regions that are necessary for stable association with SMRT, and a C-terminus helix essential for ligand-dependent dissociation of the corepressor. SMRT and N-CoR contains two independent receptor interacting domains and multiple repressor sequences. We demonstrated that overexpression of SMRT enhanced transcriptional repression of nature RA-responsive promoters.
- Anatomy and Physiology
- Medicine and Medical Research