Properties of estrogen and hydroxysteroid sulphotransferases in human mammary cancer.
Partial purification (approximately x 140-fold) of estrogen sulphotransferase (EC 2.8.2.4) in human mammary estrogen receptor positive cancer tissue was achieved by affinity chromatography on adenosine-3',5'-diphosphate-agarose. It had a Mr of approximately 70,000 by gel filtration and upon electrophoresis on concave gradient polyacrylamide gels, showed a major (Mr 70,000) and a minor (Mr 200,000) peak of activity. Kinetics of this preparation (estradiol-17 beta and estrone as substrates), and also that of hydroxysteroid sulphotransferase (EC 2.8.2.2) contained in the cytosol of human mammary cancer MCF-7 cells (5-androstene-3 beta,17 beta-diol and dehydroepiandrosterone as substrates), were compared. The enzymes showed very similar behaviour, characterized by high affinity for their steroid substrates (low nM range) and co-operativity in their binding. For hydroxysteroid sulphotransferase, the adrenal-derived estrogen 5-androstene-3 beta,17 beta-diol was the preferred substrate compared to dehydro-epiandrosterone in the 0-40 nM concentration range. Such properties of the enzymes might be designed to limit the exposure of nuclear receptor to free ligand. Alternatively, a defined subcellular location would perhaps involve the enzymes in the elimination of estrogen after processing of the ligand-bound receptor.
Adams
J B
JB
School of Biochemistry, University of New South Wales, Sydney, Australia.
Phillips
N S
NS
D001943:Breast Neoplasms / Q000201:enzymology* / Q000378:metabolism; D002460:Cell Line; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D011960:Receptors, Estrogen / Q000302:isolation & purification*; D013379:Substrate Specificity; D015238:Sulfotransferases; D013466:Sulfurtransferases / Q000302:isolation & purification*
D011960:Receptors, Estrogen; D013466:Sulfurtransferases; D015238:Sulfotransferases; C028152:alcohol sulfotransferase; C020122:estrone sulfotransferase