Dehydroepiandrosterone stimulates proliferation and gene expression in MCF-7 cells after conversion to estradiol

Mol Cell Endocrinol. 2001 Feb 28;173(1-2):1-13. doi: 10.1016/s0303-7207(00)00442-1.

Abstract

Dehydroepiandrosterone (DHEA) is a mitogen for estrogen-dependent MCF-7 breast cancer cells. Our aims were to determine whether DHEA required conversion to estrogens in order to stimulate cell proliferation and estrogen-dependent gene expression. After incubation of cells with 100 nM DHEA for 4 days, estradiol was present in the medium at a concentration of approximately 200 pM. Other compounds identified were testosterone ( approximately 300 pM) and estrone. Significant stimulation of cell proliferation by 1 nM estradiol and 100 nM DHEA was observed after 38 h and 4 days of incubation, respectively, indicating the necessity of DHEA conversion. DHEA doses > or = 10 nM induced estrogen-dependent reporter gene expression in MCF-7 cells transfected with a luciferase reporter gene under the control of the estrogen response element. DHEA-dependent stimulation of proliferation and luciferase induction could be inhibited by the anti-estrogens ICI182,780 and tamoxifen, respectively, and by the aromatase inhibitor 4-hydroxyandrostenedione. An androgenic effect of DHEA on proliferation and gene expression of MCF-7 cells was not observed. We conclude that conversion of DHEA to estrogens, particularly estradiol, is required to exert a mitogenic response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstenedione / analogs & derivatives*
  • Androstenedione / pharmacology
  • Antineoplastic Agents, Hormonal / pharmacology
  • Aromatase / metabolism
  • Aromatase Inhibitors
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • Chromatography, Thin Layer
  • Dehydroepiandrosterone / metabolism*
  • Dehydroepiandrosterone / pharmacology*
  • Dexamethasone / pharmacology
  • Dihydrotestosterone / pharmacology
  • Estradiol / analogs & derivatives*
  • Estradiol / metabolism*
  • Estradiol / pharmacology
  • Estrogen Antagonists / pharmacology
  • Female
  • Fulvestrant
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Immunoassay
  • Mitogens / pharmacology
  • Tamoxifen / pharmacology
  • Transcriptional Activation / drug effects
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Hormonal
  • Aromatase Inhibitors
  • Estrogen Antagonists
  • Mitogens
  • Dihydrotestosterone
  • Tamoxifen
  • Fulvestrant
  • Androstenedione
  • Dehydroepiandrosterone
  • Estradiol
  • Dexamethasone
  • Aromatase
  • formestane