Expression of hydroxysteroid sulphotransferase is related to estrogen receptor status in human mammary cancer

Abstract

A positive correlation between the expression of estrogen sulphotransferase (EC 2.8:2.4) and the estrogen receptor (ER) in human breast cancer tissues was previously demonstrated. We have now established that a similar correlation exists between the expression of hydroxysteroid sulphotransferase (EC 2.8:2.2) and ER in such tissues. Enzyme activity was present in 93% of the ER + tumor cytosols (mean 59 ± 44 (SD) pmol dehydroepiandrosterone sulphate formed per mg protein per 2 h ( n = 42). Activity was detected in 68% of ER— tumours and this was significantly lower (mean 21 ± 26 (SD) ( n = 19), P < 0.001) than the former group. Metabolism of estradiol-17β (E 2) and the adrenal-derived estrogen 5-androstene-3β,17β-diol (ADIOL), which is a substrate for hydroxysteroid sulphotransferase but not estrogen sulphotransferase, was studied in four ER+ human mammary cancer cell lines (MCF-7, T47-D, MDA-MB-361 and ZR-75-1) and four ER− human mammary cell lines (BT-20, MDA-MB-231, MDA-MB-330 and HBL-100), employing steroid concentrations of 1 nM. At this concentration, formation of ester sulphates was a major route of metabolism in the ER+ cell lines; E 2 yielding a mean of 6.5 pmol estrogen monosulphates/mg DNA in 16 h and ADIOL yielding a mean of 9.4 pmol C 19-5-ene steroid monosulphates/mg DNA in 16 h. In three of the four ER— cell lines, formation of sulphates from E 2 occurred at an eight-fold lower rate (mean 0.8 pmol estrogen sulphates/mg DNA in 16h), whereas MDA-MB-330 cells did not form estrogen sulphates. Only one of the four ER — cell lines (BT-20) sulphurylated ADIOL and this was at a 12-fold lower rate compared to the mean value for the ER + cell lines. Oxidation of E 2 and ADIOL occurred in all cell lines and was generally the major route of metabolism in the ER— cells. A significant correlation between formation of estrone and dehydroepiandrosterone occurred for all cell lines ( r = 0.98, P < 0.001) indicating that the same 17β-hydroxysteroid dehydrogenase was probably involved. Since ADIOL is estrogenic in a number of systems at the concentration found in the blood of Western women ( ∼ 2 nM), the coordinated expression of hydroxysteroid sulphotransferase, estrogen sulphotransferse, and ER, supports the concept of a functional relationship between estrogen action via ER and sulphurylation reactions.