title: Progestogens and membrane-initiated effects on the proliferation of human breast cancer cells.
abstract: OBJECTIVE
  Evidence is accumulating that progestogens may play a crucial role in the development of breast cancer under contraception and hormone therapy in reproductive and menopausal women. 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 progesterone and nine synthetic progestins on MCF-7 breast cancer cells overexpressing PGRMC1.
  
  
  METHODS
  MCF-7 cells were stably transfected with PGRMC1 expression plasmid (WT-12). To test the effects of progestogerone (P) and the synthetic progestins chlormadinone acetate (CMA), desogestrel (DSG), drospirenone (DRSP), dydrogesterone (DYD), levonorgestrel (LNG), medroxyprogesterone acetate (MPA), nomegestrol (NOM) and norethisterone (NET) on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations (0.01-1 µmol/l).
  
  
  RESULTS
  In MCF-7 cells, DRSP, DSG, DYD, LNG and NET increased the proliferation at 1 µmol/l, the effect being highest for NET with about 20%. In WT-12 cells, the same progestins, but additionally MPA, showed a significant increase, which was much higher (30-245%) than in MCF-7 cells. Here again, NET showed the highest proliferative effect. No effect was found for CMA, NOM and P.
  
  
  CONCLUSIONS
  Some synthetic progestins trigger a proliferative response of PGRMC1-overexpressed MCF-7 cancer cells. The effect of progestogens on breast cancer tumorigenesis may clearly depend on the specific pharmacology of the various synthetic progestins.
authors.affiliation: Beijing Ob/Gyn Hospital, Capital Medical University, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Ruan
authors.forename: H
authors.initials: H
authors.lastname: Neubauer
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Schneck
authors.forename: S
authors.initials: S
authors.lastname: Schultz
authors.forename: T
authors.initials: T
authors.lastname: Fehm
authors.forename: M A
authors.initials: MA
authors.lastname: Cahill
authors.forename: H
authors.initials: H
authors.lastname: Seeger
authors.forename: A O
authors.initials: AO
authors.lastname: Mueck
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002462:Cell Membrane / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D015870:Gene Expression; D006801:Humans; D061986:MCF-7 Cells; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D009640:Norethindrone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000235:genetics / Q000502:physiology; D014162:Transfection
chemical_list: D008565:Membrane Proteins; C115296:PGRMC1 protein, human; D045167:Progesterone Congeners; D011372:Progestins; D011980:Receptors, Progesterone; D011374:Progesterone; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone