Progesterone receptor downregulates breast cancer resistance protein expression via binding to the progesterone response element in breast cancer.

Cancer Science
Xiaojuan WuGengyin Zhou

Abstract

Breast cancer resistance protein (BCRP) plays a major role in multidrug resistance (MDR). Sequence analysis reveals there is a novel progesterone response element (PRE) in the BCRP promoter, suggesting progesterone receptor (PR) may have a function in the regulation of BCRP expression. We examined the expressions of BCRP, PR, estrogen receptor α (ERα), androgen receptor (AR) and Her-2 in 95 breast cancer samples by immunohistochemistry. Then, to identify the role of PR in the regulation of BCRP expression, two constructs encoding full length BCRP cDNA driven by putative PRE promoter or constitutive CMV promoter were transfected into MCF-7 and MDA-MB-231, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to detect the expression of BCRP. Further electrophoretic mobility shift assay (EMSA) was used to verify the nuclear protein-DNA specific binding. We innovatively found that the expression of BCRP negatively related with that of PR and ERα in breast cancer by immunohistochemistry. While at a cellular level, after being treated by progesterone and 17β-estradiol, BCRP mRNA and protein levels were significantly reduced in a concentration-dependent manner in MCF-7/P-BCRP cells with...Continue Reading

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Citations

Dec 25, 2012·Yi chuan = Hereditas·Xin-Gang WuQian Huang
Jan 8, 2013·Expert Opinion on Drug Metabolism & Toxicology·Rebecca Schnepf, Oliver Zolk
Sep 22, 2017·Current Medicinal Chemistry·Juan Pablo RigalliJohanna Weiss
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