The great majority of breast
cancers are in their early stage
hormone-dependent and it is well accepted that
estradiol (E(2)) plays an important role in the genesis and evolution of this
tumor. Human
breast cancer tissues contain all the
enzymes:
estrone sulfatase, 17 beta-
hydroxysteroid dehydrogenase (17 beta-HSD),
aromatase, involved in the last steps of E(2) bioformation in this tissue. Quantitative data show that the '
sulfatase pathway', which transforms
estrogen sulfates into the bioactive unconjugated E(2), is 100-500 times higher than the '
aromatase pathway' which converts
androgens into
estrogens. In this paper we explore the effect of E(2) on the
sulfatase activity using two
hormone-dependent human
breast cancer cells: MCF-7 and T-47D. The action of E(2) on the
sulfatase activity was evaluated by the conversion of
estrone sulfate (E(1)S) into E(2). The cells were incubated in Minimal Essential Medium (MEM) containing 5%
steroid-depleted
fetal calf serum and incubated with physiological concentrations of [(3)H]E(1)S (5 x 10(-9) M) alone (control) or in the presence of E(2) (5 x 10(-10) to 5 x 10(-5) M) for 24 h at 37 degrees C. It was found that E(2) is a potent inhibitory agent of the
estrone sulfatase activity in both cell lines. A low concentration of E(2): 5 x 10(-9) M decreases the
sulfatase activity by 67% in MCF-7 cells and 57% in T-47D cells. More than 80% of the decrease in the formation of E(2) was obtained with the dose of 5 x 10(-7) M in both cell lines. It is concluded that this paradoxical effect of E(2) adds a new
biological response of this
hormone and could be related to
estrogen replacement therapy in which it was observed to have either no effect or to decrease
breast cancer mortality in postmenopausal women. Preliminary results are indicated in the Proceedings of the 14th International Symposium of the Journal of
Steroid Biochemistry & Molecular Biology (Quebec, Canada, 24-27 June 2000) [J.
Steroid Biochem. Molec. Biol. 76 (2001) 95-104](1) and presented at the 83rd Annual Meeting of the Endocrine Society (Denver, USA, 20-23 June 2001 (abstract no. P2-615).