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Updated: Jul 10, 2026
16:24
Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
Published on: February 21, 2014
A repressive role for prohibitin in estrogen signaling
Bin He1, Qin Feng, Atish Mukherjee
1Department of Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Molecular Endocrinology (Baltimore, Md.)
|October 13, 2007
Summary
Prohibitin (PHB) acts as a transcriptional corepressor for estrogen receptor alpha (ERalpha). PHB forms complexes with REA, which limits its corepressor activity, impacting gene expression and mammary gland development.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- Nuclear receptor-mediated gene expression relies on coregulators.
- Prohibitin (PHB) is implicated as a tumor suppressor.
- Estrogen receptor alpha (ERalpha) is a key regulator in many biological processes.
Purpose of the Study:
- To investigate the role of prohibitin (PHB) in nuclear receptor-mediated gene expression.
- To determine if PHB functions as a corepressor for ERalpha.
- To elucidate the mechanism of PHB's interaction with other proteins and its functional consequences.
Main Methods:
- Overexpression and depletion of PHB in MCF-7 breast cancer cells.
- Chromatin immunoprecipitation to assess promoter association.
- Co-immunoprecipitation to study protein interactions.
- Analysis of heterozygous PHB null mice for developmental phenotypes.
Main Results:
- PHB inhibits ERalpha transcriptional activity; PHB depletion enhances ERalpha target gene expression.
- PHB associates with the pS2 promoter and dissociates upon estradiol treatment.
- PHB forms stable heteromers with REA, and this interaction modulates their corepressor activity.
- PHB ablation leads to embryonic lethality; heterozygous mice show mammary gland hyperplasia.
Conclusions:
- PHB functions as a transcriptional corepressor for ERalpha in vitro and in vivo.
- Heteromerization of PHB with REA is a novel mechanism to regulate PHB's corepressor activity.
- Dysregulation of PHB impacts gene expression and development, with implications for cancer and embryogenesis.
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