Paradoxical effect of estradiol: it can block its own bioformation in human breast cancer cells

The great majority of breast cancers are in their early stage hormone-depen dent and it is well accepted that estradiol (E-2) Plays an important role i n the genesis and evolution of this tumor. Human breast cancer tissues cont ain all the enzymes: estrone sulfatase, 17 beta -hydroxysteroid dehydrogena se (17 beta -HSD), aromatase, involved in the last steps of E, bioformation in this tissue. Quantitative data show that the 'sulfatase pathway', which transforms estrogen sulfates into the bioactive, unconjugated E, is 100-50 0 times higher than the 'aromatase pathway' which converts androgens into e strogens. In this paper we explore the effect of E2 on the sulfatase activi ty using two hormone-dependent human breast cancer cells: MCF-7 and T-47D. The action of E2 on the sulfatase activity was evaluated by the conversion of estrone sulfate (E,S) into E2. The cells were incubated in Minimal Essen tial Medium (MEM) containing 5% steroid-depleted fetal calf serum and incub ated with physiological concentrations of [H-3]E1S (5 x 10(-9) M) alone (co ntrol) or in the presence of E2 (5 x 10(-10) to 5 x 10(-5) M) for 24 h at 3 7 degrees C. It was found that E, is a potent inhibitory agent of the estro ne sulfatase activity in both cell lines. A low concentration of E,: 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 E2 was obtaine d with the dose of 5 x 10(-7) M in both cell lines. It is concluded that th is paradoxical effect of E2 adds a new biological response of this hormone and could be related to estrogen replacement therapy in which it was observ ed to have either no effect or to decrease breast cancer mortality in postm enopausal women. Preliminary results are indicated in the Proceedings of th e 14th International Symposium of the Journal of Steroid Biochemistry & Mol ecular 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 t he Endocrine Society (Denver, USA, 20-23 June 2001 (abstract no. P2-615). ( C) 2001 Elsevier Science Ltd. All rights reserved..