4-Hydroxylation of estrogens as marker of human mammary tumors.
Estrogen is a known risk factor in human breast cancer. In rodent models, estradiol has been shown to induce tumors in those tissues in which this hormone is predominantly converted to the catechol metabolite 4-hydroxyestradiol by a specific 4-hydroxylase enzyme, whereas tumors fail to develop in organs in which 2-hydroxylation predominates. We have now found that microsomes prepared from human mammary adenocarcinoma and fibroadenoma predominantly catalyze the metabolic 4-hydroxylation of estradiol (ratios of 4-hydroxyestradiol/2-hydroxyestradiol formation in adenocarcinoma and fibroadenoma, 3.8 and 3.7, respectively). In contrast, microsomes from normal tissue obtained either from breast cancer patients or from reduction mammoplasty operations expressed comparable estradiol 2- and 4-hydroxylase activities (corresponding ratios, 1.3 and 0.7, respectively). An elevated ratio of 4-/2-hydroxyestradiol formation in neoplastic mammary tissue may therefore provide a useful marker of benign or malignant breast tumors and may indicate a mechanistic role of 4-hydroxyestradiol in tumor development.
Liehr
J G
JG
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555-1031, USA.
Ricci
M J
MJ
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000737:chemistry / Q000378:metabolism*; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D004967:Estrogens / Q000737:chemistry / Q000378:metabolism*; D002393:Estrogens, Catechol / Q000378:metabolism; D005260:Female; D018226:Fibroadenoma / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D008861:Microsomes / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism
D014408:Biomarkers, Tumor; D004967:Estrogens; D002393:Estrogens, Catechol; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; C001390:2-hydroxyestradiol; C014036:4-hydroxyestradiol; D013250:Steroid Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C020120:estrogen 2-hydroxylase