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 characte rized in our own laboratory, were used to study both oxidative and red uctive pathways of 17-beta-hydroxysteroid dehydrogenase (17beta-OH-SDH ). This enzyme has been suggested to catalyze conversion of both estro ne to estradiol and estradiol to estrone. In order to determine the na tural preferred enzymic pathway, the enzymic activity was assayed in i ntact cell monolayers. In these cells, reduction of estrone to estradi ol was 7-fold higher than oxidation of estradiol to estrone. For the r eductive pathway, the apparent Michaelis-Menten (K(m)) was 5.5 muM, an d for the oxidative pathway, it was 14.3 muM. The enzymic conversion o f estrone to estradiol was enhanced by 72 h treatment with estrone, es tradiol and R5020, dehydroepiandrosterone, or dehydroepiandrosterone s ulfate. On the other hand, oxidation of estradiol to estrone was stimu lated by estradiol + R5020, but inhibited by estrone treatment. The re sults of the kinetic study, and regulation by various steroids in the present study, indicate that oxidation of estradiol or reduction of es trone is probably mediated via different forms of 17beta-OH-SDH.