Metabolism of estradiol by human breast cancer.
The activities of estrogen-2,4- and 16 alpha-hydroxylase as well as 17 beta-hydroxysteroid dehydrogenase (17 beta-OHSDHase) were determined in normal, benign and mammary tumor breast tissues. All three hydroxylases were absent in both normal and benign tumor breast tissues. 17 beta-OHSDHase was absent from normal breast tissues but present in all benign tumor tissues. Estrogen-2-hydroxylase was present in most breast carcinomas, was significantly higher in estrogen receptor (ER)-positive than ER-negative tumors, did not correlate with progesterone receptor (PR) and was significantly lower in the ER+PR- subgroup of breast cancers. 4-Hydroxylase activity did not correlate with either ER or PR content but was significantly lower in the ER+PR- subgroup of breast cancers. The activity of 16 alpha-hydroxylase was present in only 18% of all tumors investigated (9/50), did not correlate with the ER or PR content and was completely absent in the ER+PR- and ER-PR+ subgroups. The activity of 17 beta-OHSDHase was significantly higher than the estrogen hydroxylase but did not correlate with either the ER or PR content, and was not different among the ERPR tumor subgroups. The physiological role of these enzymes in the metabolism of estradiol in relation to breast cancer is discussed.
Abul-Hajj
Y J
YJ
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Minnesota, Minneapolis 55455.
Thijssen
J H
JH
Blankenstein
M A
MA
D001189:Aryl Hydrocarbon Hydroxylases; D001943:Breast Neoplasms / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D004960:Estradiol Dehydrogenases / Q000378:metabolism; D005260:Female; D006801:Humans; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D004960:Estradiol Dehydrogenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D039181:Steroid 16-alpha-Hydroxylase; C020120:estrogen 2-hydroxylase