title: Membrane-receptor initiated proliferative effects of dienogest in human breast cancer cells.
abstract: OBJECTIVE
  Dienogest (DNG) is already used in hormone therapy, since recently being also the progestogenic component of the first estradiol based contraceptive pill. Data on breast cancer risk are currently not available. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in tissues of breast cancer patients and has already been proposed as a predictor for breast cancer risk.
  
  
  METHODS
  MCF-7 cells overexpressing PGRMC1 were stimulated with DNG, medroxyprogesterone acetate (MPA), norethisterone (NET) and progesterone (P) as well as sequentially and continuously combined with estradiol (E2).
  
  
  RESULTS
  DNG and MPA alone elicited a significant proliferation at 10⁻⁶ and 10⁻⁵ M. NET increased cell proliferation at all concentrations tested whereas P showed no effect. E2 alone elicited a significant increase at 10⁻¹⁰ M, no effect was seen at 10⁻¹² M. Addition of the progestins (10⁻⁶ M) to E2 at 10⁻¹⁰ M had, compared to E2 only, no additional proliferating effect. However, at the low E2 concentration, DNG, MPA and NET significantly increased the E2-stimulated cell proliferation.
  
  
  CONCLUSIONS
  DNG increased proliferation alone and in combination with low E2 concentrations. Thus a progestogen-derived breast cancer risk in the presence of low E2 concentrations cannot be excluded at least in women overexpressing PGRMC1.
authors.affiliation: University Women's Hospital, Tübingen, Germany.
authors.forename: Helen
authors.initials: H
authors.lastname: Schneck
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Ruan
authors.forename: Harald
authors.initials: H
authors.lastname: Seeger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cahill
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Alfred O
authors.initials: AO
authors.lastname: Mueck
authors.forename: Hans
authors.initials: H
authors.lastname: Neubauer
mesh_terms: D001943:Breast Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D003271:Contraceptive Agents, Female / Q000009:adverse effects* / Q000494:pharmacology; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009277:Nandrolone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009376:Neoplasms, Hormone-Dependent / Q000139:chemically induced* / Q000378:metabolism; D009640:Norethindrone / Q000009:adverse effects / Q000494:pharmacology; D009994:Osmolar Concentration; D011374:Progesterone / Q000009:adverse effects / Q000494:pharmacology; D011372:Progestins / Q000009:adverse effects* / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis
chemical_list: D003271:Contraceptive Agents, Female; D004967:Estrogens; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C115296:PGRMC1 protein, human; D011372:Progestins; D011980:Receptors, Progesterone; D011994:Recombinant Proteins; C023635:dienogest; D011374:Progesterone; D004958:Estradiol; D009277:Nandrolone; D017258:Medroxyprogesterone Acetate; D009640:Norethindrone