Document Detail

The effect of progesterone, testosterone and synthetic progestogens on growth factor- and estradiol-treated human cancerous and benign breast cells.
MedLine Citation:
PMID:  16460873     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: 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.
Elizabeth A Krämer; Harald Seeger; Bernhard Krämer; Diethelm Wallwiener; Alfred O Mueck
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Publication Detail:
Type:  Journal Article     Date:  2006-02-07
Journal Detail:
Title:  European journal of obstetrics, gynecology, and reproductive biology     Volume:  129     ISSN:  0301-2115     ISO Abbreviation:  Eur. J. Obstet. Gynecol. Reprod. Biol.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-30     Completed Date:  2007-01-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375672     Medline TA:  Eur J Obstet Gynecol Reprod Biol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  77-83     Citation Subset:  IM    
Section of Endocrinology and Menopause, University Women's Hospital, Calwerstrasse 7, 72 076 Tuebingen, Germany.
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MeSH Terms
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
Fibroblast Growth Factor 2 / pharmacology
Hormone Replacement Therapy / adverse effects*
Insulin-Like Growth Factor I / pharmacology
Progesterone / pharmacology*
Progesterone Congeners / pharmacology*
Testosterone / pharmacology*
Reg. No./Substance:
0/Progesterone Congeners; 103107-01-3/Fibroblast Growth Factor 2; 50-28-2/Estradiol; 57-83-0/Progesterone; 58-22-0/Testosterone; 62229-50-9/Epidermal Growth Factor; 67763-96-6/Insulin-Like Growth Factor I

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