Abul-Hajj Y J, Thijssen J H, Blankenstein M A
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Minnesota, Minneapolis 55455.
Eur J Cancer Clin Oncol. 1988 Jul;24(7):1171-8. doi: 10.1016/0277-5379(88)90124-1.
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.
在正常乳腺组织、良性乳腺肿瘤组织及乳腺癌组织中测定了雌激素2,4-羟化酶、16α-羟化酶以及17β-羟类固醇脱氢酶(17β-OHSDHase)的活性。在正常乳腺组织和良性乳腺肿瘤组织中均未检测到这三种羟化酶的活性。17β-OHSDHase在正常乳腺组织中未检测到,但在所有良性肿瘤组织中均有表达。雌激素2-羟化酶在大多数乳腺癌组织中存在,在雌激素受体(ER)阳性肿瘤中显著高于ER阴性肿瘤,与孕激素受体(PR)无关,在ER+PR-亚组乳腺癌中显著降低。4-羟化酶活性与ER或PR含量均无关,但在ER+PR-亚组乳腺癌中显著降低。16α-羟化酶活性仅在18%的被研究肿瘤(9/50)中存在,与ER或PR含量无关,在ER+PR-和ER-PR+亚组中完全缺失。17β-OHSDHase的活性显著高于雌激素羟化酶,但与ER或PR含量均无关,在ERPR肿瘤亚组之间无差异。本文讨论了这些酶在雌二醇代谢中与乳腺癌相关的生理作用。