J.Jpn. Surg. Soc.. 93(5): 505-517, 1992

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Original article

BIOLOGICAL EFFECT OF ESTROGEN METABOLITES IN HUMAN BREAST CANCER

In order to investigate the estrogen metabolism in human breast cancer, the estradiol 2- and 16α-hydroxylase (2-,16α-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<0.05). Patients without lymph node metastases showed relatively higher activity than those with metastases (0.05<p<0.1). The 16α-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 16α-hydroxyestrone. The cell proliferation stimulated with 16α-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.

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