Concepedia

4-Hydroxylation of estrogens as marker of human mammary tumors.

Proceedings of the National Academy of Sciences · 1996 · 415 citations · 29 references

TL;DR

Estrogen is a known breast cancer risk factor, and rodent studies show that estradiol induces tumors in tissues where 4‑hydroxylation predominates, whereas 2‑hydroxylation predominance is associated with tumor resistance. The study proposes that an elevated 4‑/2‑hydroxyestradiol ratio in mammary tissue could serve as a marker for benign or malignant breast tumors and suggests a mechanistic role for 4‑hydroxyestradiol in tumor development. Human mammary adenocarcinoma and fibroadenoma microsomes exhibit a 4‑/2‑hydroxyestradiol ratio of ~3.8–3.7, markedly higher than the ~1.3–0.7 ratio seen in normal breast tissue microsomes.

Abstract

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.