Testosterone and 5 alpha-dihydrotestosterone inhibit in vitro growth of human breast cancer cell lines.
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.
Ortmann
J
J
Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive Medicine, Ruprecht-Karls-Universität, Heidelberg, Germany.
Prifti
S
S
Bohlmann
M K
MK
Rehberger-Schneider
S
S
Strowitzki
T
T
Rabe
T
T
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
D016895:Culture Media, Serum-Free; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone