title: Progesterone negatively regulates BCRP in progesterone receptor-positive human breast cancer cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, School of Medicine, Shandong University, Shandong, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wu
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.forename: Limin
authors.initials: L
authors.lastname: Sun
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Su
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism* / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D011374:Progesterone