C 19 steroids estrogenic activity in human breast cancer cell lines: importance of dehydroepiandrosterone sulfate at physiological plasma concentration

Abstract

The estrogenic action of C 19 steroids on breast cancer cells was measured by bioluminescence in stably transfected human breast cancer MCF-7 and T47D cell lines with a reporter gene that allows expression of the firefly luciferase enzyme under control of an estrogen regulatory element. The “estrogenic activity” of C 19 steroids, such as dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), androst-5-en-3β,17β-diol, androst-4-en-3,17-dione, dihydrotestosterone, testosterone, and 5α-androstan-3β,17β-diol was studied. This showed that DHEAS, at concentration observed in physiological conditions (10 −6 M), had a high “estrogen-like effect” in MCF-7 and T47D cell lines. Other C 19 steroids, at physiological plasma concentration, alone or together did not have any significant effect on the luciferase activity. Moreover aminoglutethimide, an inhibitor of the aromatase enzyme, in the presence of C 19 steroids, partially decreased the luciferase activity. These results suggest that MCF-7 and T47D cell lines could convert DHEAS to estrogen-like compounds by different enzymatic systems.