Androgen-induced inhibition of proliferation in human breast cancer MCF7 cells transfected with androgen receptor

Endocrinology. 1997 Apr;138(4):1406-12. doi: 10.1210/endo.138.4.5047.


Sex steroids control the proliferation of their target cells through two different pathways: 1) proliferative response (Step-1); and 2) inhibition of cell proliferation (Step-2). Mechanisms of cell proliferation regulation are incompletely understood; however, there is general agreement with the notion that sex steroid receptors play an important role in the control of the proliferation of sex steroid target cells. To test this hypothesis, a full human androgen receptor (AR) vector was transfected into human breast cancer MCF7 cells. The cloned cells that stably express the AR, called MCF7-AR1 cells, contained approximately five times more AR than the wild-type MCF7 cells from which they were derived. These AR-transfected cells retained their capacity to proliferate when estrogens were added to 10% charcoal-dextran stripped human serum but did not acquire the ability to proliferate when androgens were added to this medium. In serumless medium (ITDME), these cells proliferated maximally, as MCF7 cells did; however, natural and synthetic androgens prevented the AR-transfected cells from proliferating. Inhibition of cell proliferation occurred when physiological androgen concentrations (1 nM) were added to ITDME; this effect was almost completely reversed by Casodex, a synthetic androgen antagonist. Under the effect of androgens added to ITDME, MCF7-AR1 cells were arrested in the G0/G1 phase within 24 h. These data suggest that: 1) the androgen-induced inhibition of cell proliferation (Step-2) is AR-mediated; and 2) the AR may be necessary, but not sufficient, to mediate the androgen-induced proliferative response (Step-1).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgen Antagonists
  • Androgens / pharmacology*
  • Anilides / pharmacology
  • Blotting, Western
  • Breast Neoplasms / pathology*
  • Cell Cycle
  • Cell Division / drug effects
  • Dihydrotestosterone / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Flutamide / analogs & derivatives
  • Flutamide / pharmacology
  • Humans
  • In Vitro Techniques
  • Metribolone / administration & dosage
  • Metribolone / pharmacology
  • Nandrolone / analogs & derivatives
  • Nandrolone / metabolism
  • Nitriles
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / physiology
  • Testosterone / pharmacology
  • Testosterone Congeners
  • Tosyl Compounds
  • Transfection
  • Tumor Cells, Cultured


  • Androgen Antagonists
  • Androgens
  • Anilides
  • Nitriles
  • Receptors, Androgen
  • Testosterone Congeners
  • Tosyl Compounds
  • Dihydrotestosterone
  • Metribolone
  • hydroxyflutamide
  • Testosterone
  • Nandrolone
  • Flutamide
  • mibolerone
  • bicalutamide