Regulation of 17 beta-hydroxysteroid dehydrogenase in a newly-established human breast carcinoma cell line

UISO-BCA-1 human breast carcinoma cell lines, established and characterized in our own laboratory, were used to study both oxidative and reductive pathways of 17 beta-hydroxysteroid dehydrogenase (17 beta-OH-SDH). This enzyme has been suggested to catalyze conversion of both estrone to estradiol and estradiol to estrone. In order to determine the natural preferred enzymic pathway, the enzymic activity was assayed in intact cell monolayers. In these cells, reduction of estrone to estradiol was 7-fold higher than oxidation of estradiol to estrone. For the reductive pathway, the apparent Michaelis-Menten (Km) was 5.5 microM, and for the oxidative pathway, it was 14.3 microM. The enzymic conversion of estrone to estradiol was enhanced by 72 h treatment with estrone, estradiol and R5020, dehydroepiandrosterone, or dehydroepiandrosterone sulfate. On the other hand, oxidation of estradiol to estrone was stimulated by estradiol+R5020, but inhibited by estrone treatment. The results of the kinetic study, and regulation by various steroids in the present study, indicate that oxidation of estradiol or reduction of estrone is probably mediated via different forms of 17 beta-OH-SDH.