INFLUENCE OF ESTROGEN METABOLISM ON PROLIFERATION OF HUMAN BREAST-CANCER

In order to investigate the influence of estrogen metabolism on human breast cancer, estradiol 2- and 16 alpha-hydroxylase (2- and 16 alpha- OHase) activities were determined in the microsomal fractions of cance r tissues by using reverse phase HPLC. 2-OHase activity was detected i n most cancer tissues and noncancerous tissues, but the activity was s ignificantly lower in cancer tissues than in the paired noncancerous t issues (0.01 < p < 0.02). Interestingly the patients without lymph nod e metastasis had significantly higher 2-OHase activity in cancer tissu es than those with lymph node metastasis (0.02 < p < 0.05). No correla tion was observed between ER status and 2-OHase activity in cancer tis sues. On the other hand, 16 alpha-OHase activity was detected only in one third of the breast cancer tissues examined. The activity was not significantly different from that in noncancerous tissues, although it was relatively higher in ER-positive cancer tissues when compared wit h that in ER-negative ones (0.05 < p < 0.1). Estrone sulfatase activit y measured simultaneously in the cytosol fractions of some specimens w as much higher in cancer tissues than in noncancerous tissues (0.02 < p < 0.05). We found, however, no correlation between estrone sulfatase activity and estradiol hydroxylase activity. Taken together, our resu lts suggest that the increase in 2-OHase activity prevents the prolife ration of breast cancer and that estradiol metabolism is regulated ind ependently of the local biosynthesis of estrogen.