Importance of estrogen sulfates in breast cancer.
Estrogen sulfates are quantitatively the most important form of circulating estrogens during the menstrual cycle and in the post-menopausal period. Huge quantities of estrone sulfate and estradiol sulfate are found in the breast tissues of patients with mammary carcinoma. It has been demonstrated that different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, estriol-3-sulfate) can provoke important biological responses in different mammary cancer cell lines: there is a significant increase in progesterone receptor. On the other hand, no significant effect was observed with estrogen-17-sulfates. The reason for the biological response of estrogen-3-sulfates is that these sulfates are hydrolyzed, and no sulfatase activity for C17-sulfates is present in these cell lines. [3H]Estrone sulfate is converted in a very high percentage to estradiol (E2) in different hormone-dependent mammary cancer cell lines (MCF-7, R-27, T-47D), but very little or no conversion was found in the hormone-independent mammary cancer cell lines (MDA-MB-231, MDA-MB-436). Different anti-estrogens (tamoxifen and derivatives) and another potent anti-estrogen: ICI 164,384, decrease the concentration of estradiol very significantly after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect was observed for the uptake and conversion of estrone sulfate in the hormone-independent mammary cancer cell lines. Progesterone provokes an important decrease in the uptake and in estradiol levels after incubation of [3H]estrone sulfate with the MCF-7 cells. It is concluded that in breast cancer: (1) Estrogen sulfates can play an important role in the biological response of estrogens; (2) Anti-estrogens and progesterone significantly decrease the uptake and estradiol levels in hormone-dependent mammary cancer cell lines; (3) The control of the sulfatase and 17 beta-hydroxysteroid dehydrogenase activities, which are key steps in the formation of estradiol in the breast, can open new possibilities in the treatment of hormone-dependent mammary cancer.
Pasqualini
J R
JR
C.N.R.S. Steroid Hormone Research Unit, Foundation for Hormone Research, Paris, France.
Gelly
C
C
Nguyen
B L
BL
Vella
C
C
D001943:Breast Neoplasms / Q000503:physiopathology*; D002460:Cell Line; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D004966:Estrogens, Conjugated (USP); D005260:Female; D006801:Humans; D008597:Menstrual Cycle; D013431:Sulfates; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004965:Estrogen Antagonists; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D013431:Sulfates