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 or...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-04, Vol.93 (8), p.3294-3296
Main Authors: Liehr, Joachim G., Ricci, Mary Jo
Format: Article
Language:English
Subjects:
Adenocarcinoma
Adenocarcinoma - metabolism
Animals
Biomarkers, Tumor - chemistry
Biomarkers, Tumor - metabolism
Breast - metabolism
Breast cancer
Breast Neoplasms - metabolism
Catechols
Cytochrome P-450 CYP1A1
Cytochrome P-450 Enzyme System - metabolism
Enzymes
Estradiol - analogs & derivatives
Estradiol - metabolism
Estrogens
Estrogens - chemistry
Estrogens - metabolism
Estrogens, Catechol - metabolism
Female
Fibroadenoma
Fibroadenoma - metabolism
Humans
Hydroxylation
In Vitro Techniques
Medical research
Microsomes
Microsomes - metabolism
Rodents
Steroid Hydroxylases - metabolism
Tissue samples
Tumors
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.8.3294