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The effect of progesterone, testosterone and synthetic progestogens on growth factor- and estradiol-treated human cancerous and benign breast cells.

AbstractOBJECTIVE:
The effects of progesterone (P), testosterone (T), chlormadinone acetate (CMA), medroxyprogesterone acetate (MPA), norethisterone (NET), levonorgestrel (LNG), dienogest (DNG), gestodene (GSD) and 3-ketodesogestrel (KDG) were investigated in normal human breast epithelial MCF10A cells. In addition, the effects of these steroids were tested in estrogen and progesterone receptor positive HCC1500 human primary breast cancer cells.
STUDY DESIGN:
MCF10A cells were incubated with each progestogen at 1 microM and 100 nM for 7 days with growth factors epidermal growth factor (EGF), fibroblast growth factor (FGF) and insulin-like growth factor (IGF-I) (GFs, each 1 pM), and HCC1500 cells with GFs and/or estradiol (E2) 100 pM. Cell proliferation rate was measured by ATP-assay and cell death by photometric enzyme immunoassay. Ratios of cell death:proliferation were calculated.
RESULTS:
MPA and CMA with GFs induced proliferation of MCF10A cells. P, T, NET, LNG, DNG, GSD and KDG had no significant effect. In HCC1500 cells, MPA and CMA with GFs had an inhibitory effect compared to GFs alone. NET, LNG, DNG, GSD, KDG and T enhanced the proliferative effect of GFs. P had no significant effect. No progestogen could further enhance the stimulatory effect of E2 on HCC1500 cells; all but KDG inhibited it. MPA, GSD, T, CMA and NET had an anti-proliferative effect on the mitotic GF and E2 combination. P, LNG, DNG and KDG had no significant effect.
CONCLUSIONS:
Estrogens and mitogenic growth factors from stromal breast tissue are significant in growth-regulation of breast cells and may alter responses to progestogens. Certain progestogens are able to induce proliferation of or inhibit growth of benign or malignant human breast epithelial cells independently of the effects of growth factors and E2; therefore, choice of progestogen for hormone therapy may be important in terms of influencing possible breast cancer risk.
AuthorsElizabeth A Krämer, Harald Seeger, Bernhard Krämer, Diethelm Wallwiener, Alfred O Mueck
JournalEuropean journal of obstetrics, gynecology, and reproductive biology (Eur J Obstet Gynecol Reprod Biol) Vol. 129 Issue 1 Pg. 77-83 (Nov 2006) ISSN: 0301-2115 [Print] Ireland
PMID16460873 (Publication Type: Journal Article)
Chemical References
  • Progesterone Congeners
  • Fibroblast Growth Factor 2
  • Testosterone
  • Progesterone
  • Estradiol
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
Topics
  • Breast (cytology)
  • Breast Neoplasms (metabolism)
  • Cell Death (drug effects)
  • Cell Proliferation (drug effects)
  • Cells, Cultured
  • Epidermal Growth Factor (pharmacology)
  • Epithelial Cells (drug effects)
  • Estradiol (pharmacology)
  • Female
  • Fibroblast Growth Factor 2 (pharmacology)
  • Hormone Replacement Therapy (adverse effects)
  • Humans
  • Insulin-Like Growth Factor I (pharmacology)
  • Progesterone (pharmacology)
  • Progesterone Congeners (pharmacology)
  • Testosterone (pharmacology)

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