Progesterone negatively regulates BCRP in progesterone receptor-positive human breast cancer cells.

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Wu X, Zhang X, Sun L, Zhang H, Li L, Wang X, Li W, Su P, Hu J, Gao P, Zhou G

Progesterone negatively regulates BCRP in progesterone receptor-positive human breast cancer cells.

Cell Physiol Biochem. 2013;32(2):344-54. doi: 10.1159/000354442. Epub 2013 Aug 14.

PubMed ID

23988382 [ View in PubMed

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Abstract

BACKGROUND/AIMS: Breast cancer resistance protein (BCRP) plays a crucial role in multidrug resistance (MDR). Previous studies have shown that steroid hormones, like progesterone (PROG), regulate BCRP expression. The presence of a progesterone response element (PRE) in the BCRP promoter, suggests that PROG may regulate transcription of BCRP. METHODS: To investigate the role of PROG in the regulation of BCRP expression, two constructs encoding full-length BCRP driven by either an endogenous PRE promoter or a constitutive CMV promoter, were transfected into T47D cells that express the progesterone receptor (PR) or into PR-negative MDA-MB-231 cells. RESULTS: After treatment with PROG, qPCR and Western blotting analyses indicated that BCRP mRNA and BCRP protein levels were significantly reduced in a dose-dependent manner in PR-positive cells, but PROG had no significant effect on BCRP levels in the PR-negative cells. The effect observed in PR-positive cells was reversed by co-treatment with RU-486, a specific PROG inhibitor. Cytometric analysis confirmed that BCRP-mediated drug efflux was inhibited and chemosensitivity to mitoxantrone was markedly increased by PROG treatment. CONCLUSION: These results suggest that PROG reverses BCRP-mediated MDR by down-regulating BCRP expression in breast cancer cells by affecting transcription from the PRE-containing BCRP promoter. Our studies suggest that breast cancer patients with BCRP-mediated MDR may be successfully treated with PROG.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Progesterone	ATP-binding cassette sub-family G member 2	Protein	Humans	Unknown	Inhibitor Inducer	Details