title: The presence of a membrane-bound progesterone receptor sensitizes the estradiol-induced effect on the proliferation of human breast cancer cells.
abstract: OBJECTIVE
  Breast cancer risk is still an important topic regarding hormone therapy as well as oral contraception. Evidence that progestogens may play a crucial role is accumulating. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of different estradiol (E2) concentrations and the addition of two progestogens on MCF-7 breast cancer cells overexpressing PGRMC1.
  
  
  METHODS
  MCF-7 cells were stably transfected with PGRMC1 expression plasmid (MCF-7/PGRMC1-3HA [WT-12]). To test the effects of E2 and progestogens on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations of E2 (10 and 10 M) alone and in combination with progesterone and medroxyprogesterone acetate (each 10 M).
  
  
  RESULTS
  E2 elicited a concentration-dependent proliferative effect on both cell lines, which was much more pronounced in WT-12 cells (50% vs 200%). This effect could be completely abrogated by the addition of the E2 antagonist fulvestrant. Addition of progesterone had no influence on the E2-induced effect, whereas medroxy-progesterone acetate enhanced the E2-induced effect at a low E2 concentration, which was, again, more pronounced in the WT-12 cells. The figures were between 20% and 40% in MCF-7 and between 60% and 250% in WT-12 cells.
  
  
  CONCLUSIONS
  Overexpression of PGRMC1 sensitizes the proliferative response of the MCF-7 breast cancer cell line to estradiol. The effect of progestogens on breast cancer tumorigenesis may depend on the specific progestogen used for hormone therapy or oral contraception.
authors.affiliation: University Women's Hospital, Tuebingen, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Neubauer
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Harald
authors.initials: H
authors.lastname: Seeger
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cahill
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tong
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Ruan
authors.forename: Alfred O
authors.initials: AO
authors.lastname: Mueck
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003271:Contraceptive Agents, Female / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*
chemical_list: D003271:Contraceptive Agents, Female; D008565:Membrane Proteins; C115296:PGRMC1 protein, human; D011980:Receptors, Progesterone; D000077267:Fulvestrant; D004958:Estradiol; D017258:Medroxyprogesterone Acetate