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Biochem Biophys Res Commun. 2014 Sep 26;452(3):840-4. doi: 10.1016/j.bbrc.2014.09.017. Epub 2014 Sep 16.

Human glutathione S-transferase P1-1 functions as an estrogen receptor α signaling modulator.

Author information

1
Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
2
Department of Food and Nutrition, College of Life Science, Sookmyung Women's University, Seoul, Republic of Korea.
3
Department of Pharmacy, College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea.
4
Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women's University, Seoul, Republic of Korea. Electronic address: minsunchang@sm.ac.kr.

Abstract

Estrogen receptor α (ERα) plays a crucial role in estrogen-mediated signaling pathways and exerts its action as a nuclear transcription factor. Binding of the ligand-activated ERα to the estrogen response element (ERE) is a central part of ERα-associated signal transduction pathways and its aberrant modulation is associated with many disease conditions. Human glutathione S-transferase P1-1 (GSTP) functions as an enzyme in conjugation reactions in drug metabolism and as a regulator of kinase signaling pathways. It is overexpressed in tumors following chemotherapy and has been associated with a poor prognosis in breast cancer. In this study, a novel regulatory function of GSTP has been proposed in which GSTP modulates ERE-mediated ERα signaling events. Ectopic expression of GSTP was able to induce the ERα and ERE-mediated transcriptional activities in ERα-positive but GSTP-negative MCF7 human breast cancer cells. This inductive effect of GSTP on the ERE-transcription activity was diminished when the cells express a mutated form of the enzyme or are treated with a GSTP-specific chemical inhibitor. It was found that GSTP inhibited the expression of the receptor interacting protein 140 (RIP140), a negative regulator of ERα transcription, at both mRNA and protein levels. Our study suggests a novel non-enzymatic role of GSTP which plays a significant role in regulating the classical ERα signaling pathways via modification of transcription cofactors such as RIP140.

KEYWORDS:

Breast cancer; Estrogen receptor α; Estrogen response element; Glutathione S-transferase P1-1; Regulatory interacting protein 140

PMID:
25218501
DOI:
10.1016/j.bbrc.2014.09.017
[Indexed for MEDLINE]

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