Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 392, Issue 3, Pages 357-362Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.01.025
Keywords
DBC1; ER beta; Breast cancer; Transcription; Repression
Categories
Funding
- Ministry of Education, Science and Culture
- JMS Bayer Schering Pharma
- Kowa Life Science Foundation, Japan
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It has been well established that estrogen is involved in the pathophysiology of breast cancer Estrogen receptor (ER) alpha appears to promote the proliferation of cancer tissues, while ER beta can protect against the mitogenic effect of estrogen in breast tissue The expression status of ER alpha and ER beta may greatly influence on the development, treatment, and prognosis of breast cancer Previous studies have indicated that the deleted in breast cancer 1 (DBC1/KIAA1967) gene product has roles in regulating functions of nuclear receptors The gene encoding DBC1 is a candidate for tumor suppressor identified by genetic search for breast cancer Caspase-dependent processing of DBC1 promotes apoptosis. and depletion of the endogenous DBC1 negatively regulates p53-dependent apoptosis through its specific inhibition of SIRT1 In addition, DBC1 modulates ER alpha expression and promotes breast cancer cell Survival by binding to ER alpha Here we report an ER beta-specific repressive function of DBC1 immunoprecipitation and immunofluorescence studies show that ER beta and DBC1 interact in a ligand-independent manner similar to ER alpha. In vitro pull-down assays revealed a direct interaction between DBC1 ammo-terminus and activation function-1/2 domain of ER beta Although DBC1 shows no influence on the ligand-dependent transcriptional activation function of ER alpha, the expression of DBC1 negatively regulates the ligand-dependent transcriptional activation function of ER beta in vivo, and RNA interference-mediated depletion of DBC1 stimulates the transactivation function of ER beta These results implicate the principal role of DBC1 in regulating ER beta-dependent gene expressions (C) 2010 Elsevier Inc. All rights reserved
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