title: Nomegestrol acetate sequentially or continuously combined to estradiol did not negatively affect membrane-receptor associated progestogenic effects in human breast cancer cells.
abstract: OBJECTIVE
  Recently the first monophasic contraceptive pill containing estradiol has been developed which is thought to be a milestone in contraception. Nomegestrol acetate (NOM) is the progestogenic component. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in the tissue of breast cancer patients, and can predict a progestogen dependent risk of breast cancer.
  
  
  METHODS
  MCF-7 cells were transfected with PGRMC1 expression plasmid, and were stimulated with estradiol (E2, 10(-12) and 10(-10) M). NOM, progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) (each 10(-7) M) were added sequentially or continuously.
  
  
  RESULTS
  E2 at 10(-10) M elicited a significant increase of cell proliferation from 150 to 200%. No effect was seen at 10(-12) M. Addition of the progestogens to E2 at 10(-10) M had no significant effect. However, at an E2 10(-12) M, NET significantly stimulated cell proliferation more pronounced in the continuous combined model. No effect was seen for NOM, P and MPA. The E2/NET combined effect could be abrogated by the addition of an estrogen receptor (ER) antagonist.
  
  
  CONCLUSIONS
  Since NOM did not increase proliferation it may be concluded that it will be neutral in terms of breast cancer risk when combined with E2 at least in women overexpressing PGRMC1.
authors.affiliation: Beijing Ob/Gyn Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiangyan
authors.initials: X
authors.lastname: Ruan
authors.forename: Helen
authors.initials: H
authors.lastname: Schneck
authors.forename: Silke
authors.initials: S
authors.lastname: Schultz
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cahill
authors.forename: Harald
authors.initials: H
authors.lastname: Seeger
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Yu
authors.forename: Alfred O
authors.initials: AO
authors.lastname: Mueck
authors.forename: Hans
authors.initials: H
authors.lastname: Neubauer
mesh_terms: D001940:Breast / Q000187:drug effects*; D001943:Breast Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008535:Megestrol / Q000009:adverse effects*; D008565:Membrane Proteins / Q000378:metabolism*; D009649:Norpregnadienes / Q000009:adverse effects*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013256:Steroids / Q000009:adverse effects
chemical_list: D003278:Contraceptives, Oral, Hormonal; D008565:Membrane Proteins; D009649:Norpregnadienes; C115296:PGRMC1 protein, human; D011980:Receptors, Progesterone; D013256:Steroids; C038501:nomegestrol acetate; D008535:Megestrol