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
cancer tissues by using reverse phase HPLC. 2-OHase activity was detected in most
cancer tissues and noncancerous tissues, but the activity was significantly lower in
cancer tissues than in the paired noncancerous tissues (0.01 < p < 0.02). Interestingly the patients without
lymph node metastasis had significantly higher 2-OHase activity in
cancer tissues than those with
lymph node metastasis (0.02 < p < 0.05). No correlation was observed between ER status and 2-OHase activity in
cancer tissues. 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 with that in ER-negative ones (0.05 < p < 0.1).
Estrone sulfatase activity measured simultaneously in the cytosol fractions of some specimens was 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 results suggest that the increase in 2-OHase activity prevents the proliferation of
breast cancer and that
estradiol metabolism is regulated independently of the local biosynthesis of
estrogen.