[Biological effect of estrogen metabolites in human breast cancer].
In order to investigate the estrogen metabolism in human breast cancer, the estradiol 2- and 16 alpha-hydroxylase (2-, 16 alpha-OHase) activities were determined in the microsomal fractions of human breast tissues by using reverse-phase HPLC. The effects of estrogen metabolites on the cell proliferation were also examined by employing two human breast cancer cell lines. The 2-OHase activity was detected in most cancerous and noncancerous tissues, but the value in cancerous tissues was significantly lower than that in noncancerous tissues (p less than 0.05). Patients without lymph node metastases showed relatively higher activity than those with metastases (0.05 less than p less than 0.1). The 16 alpha-OHase activity was, however, found in only 23% of cancerous tissues. Among those, the activity was present in 52% of ER positive cancerous tissues, but almost absent in ER negative ones. The growth ER positive cell line, MCF-7, was suppressed with 2-hydroxyestrone and stimulated with 16 alpha-hydroxyestrone. The cell proliferation stimulated with 16 alpha-hydroxyestrone was not inhibited by the addition of tamoxifen, a strong antagonist of estradiol. Two metabolites had no effect on the growth of ER negative cell line, MDA-MB-231. These results suggest that estrogen metabolites influence the proliferation of human breast cancer cells as the endogenous regulatory factors and should be considered for the future endocrine therapy.
Imoto
S
S
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000494:pharmacology*; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D004967:Estrogens; D006894:Hydroxyestrones; D011960:Receptors, Estrogen; C026702:16-hydroxyestrone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D039181:Steroid 16-alpha-Hydroxylase; C020120:estrogen 2-hydroxylase; C024980:2-hydroxyestrone