title: Testosterone and 5 alpha-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines.
abstract: Androgens are of biological and clinical importance for the growth and development of breast cancer in women, and the androgen receptor (AR) has been shown to be a predictor of tumor differentiation. In the present study, we investigated the relationship between AR status and testosterone and 5 alpha-dihydrotestosterone (DHT)-dependent proliferation of the human breast carcinoma cell lines MCF-7, T47-D, MDA-MB 435S and BT-20. AR status was studied by means of immunocytochemistry and Western blot analysis. All four cell lines stained positively for AR. Western blot analysis revealed a strong expression of AR in MCF-7, in contrast to BT-20 cells. According to proliferation kinetics, we observed a significant (p < or = 0.05) dose-dependent inhibition of cell growth by testosterone and DHT treatment in all four cell lines. In the estrogen receptor (ER)-negative cell lines BT-20 and MDA-MB 435S, testosterone was a more potent inhibitor of cell proliferation than DHT (p < or = 0.05), in contrast to the ER-positive cells lines MCF-7 and T47-D, in which a stronger inhibition of proliferation was achieved by DHT. A partial transformation of testosterone to estrogen in ER-positive cells might be an explanation for this effect. Our data favor a possible role of androgens in growth regulation of breast cancer. Clinical studies are needed to analyze the importance of AR as a possible predictor in response to endocrine therapy of breast cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, Ruprecht-Karls-Universität, Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Ortmann
authors.forename: S
authors.initials: S
authors.lastname: Prifti
authors.forename: M K
authors.initials: MK
authors.lastname: Bohlmann
authors.forename: S
authors.initials: S
authors.lastname: Rehberger-Schneider
authors.forename: T
authors.initials: T
authors.lastname: Strowitzki
authors.forename: T
authors.initials: T
authors.lastname: Rabe
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D016895:Culture Media, Serum-Free; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D011944:Receptors, Androgen / Q000032:analysis; D013739:Testosterone / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D016895:Culture Media, Serum-Free; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone