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

Dehydroepiandrosterone (DHEA) is a mitogen for estrogen-dependent MCF-7 bre ast cancer cells. Our aims were to determine whether DHEA required conversi on to estrogens in order to stimulate cell proliferation and estrogen-depen dent gene expression. After incubation of cells with 100 nM DHEA for 4 days , estradiol was present in the medium at a concentration of similar to 200 pM. Other compounds identified were testosterone (similar to 300 pM) and es trone. significant stimulation of cell proliferation by nM estradiol and 10 0 nM DHEA was observed after 38 h and 4 days of incubation, respectively, i ndicating the necessity of DHEA conversion. DHEA doses greater than or equa l to 10 nM induced estrogen-dependent reporter gene expression in MCF-7 cel ls transfected with a luciferase reporter gene under the control of the est rogen response element. DHEA-dependent stimulation of proliferation and luc iferase induction could be inhibited by the anti-estrogens IC1182,780 and t amoxifen, respectively. and by the aromatase inhibitor 4-hydroxyandrostenod ione. An androgenic effect of DHEA on proliferation and gene expression of MCF-7 cells was not observed. We conclude that conversion of DHEA to estrog ens. particularly estradiol, is required to exert a mitogenic response. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.