Metabolism and biologic response of estrogen sulfates in hormone-dependent and hormone-independent mammary cancer cell lines. Effect of antiestrogens.

Abstract

Different estrogen-3-sulfates (estrone-3-sulfate, estradiol-3-sulfate, and estriol-3-sulfate) can provoke important biologic responses in different mammary cancer cell lines; there is a significant increase in progesterone receptor. However, no significant effect was observed with estrogen-17-sulfates. The reason for the biologic 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, and T47D), but very little or no conversion was found in hormone-independent mammary cancer cell lines (MDA-MB-231 and MDA-MB-436). Different antiestrogens (tamoxifen and its derivatives) and another potent antiestrogen, ICI 164,384, significantly decrease the concentration of estradiol after incubation of estrone sulfate with the different hormone-dependent mammary cancer cell lines. No significant effect in the uptake and conversion of estrone sulfate was observed in hormone-independent mammary cancer cell lines. The data indicate that sulfatase activity for estrone sulfate is very low in the hormone-independent cell lines; however, comparative kinetic studies carried out after homogenization of MCF-7 and MDA-MB-436 cells show that sulfatase activity is similar, suggesting different mechanisms in the hydrolysis of estrone sulfate in hormone-dependent and hormone-independent cell lines. Progesterone also provokes a significant decrease in uptake and in estradiol levels after incubation of [3H]-estrone sulfate with the MCF-7 cell line. It is concluded that estrogen sulfates can play an important role in the biologic response of estrogens in breast cancer and that control of sulfatase and 17-hydroxysteroid dehydrogenase activities are key steps in the concentration and ability of estradiol in the mammary cancer cell line.

• Authors: J R Pasqualini, C Gelly, B L Nguyen
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 595 Pg. 106-16 ( 1990) ISSN: 0077-8923 [Print] United States
• PMID: 2375600 (Publication Type: Journal Article)

Chemical References

• Polyunsaturated Alkamides
• Receptors, Progesterone
• Tamoxifen
• estradiol sulfate
• Estrone
• estriol 3-sulfate
• Progesterone
• Estradiol
• ICI 164384
• Estriol
• estrone sulfate

Topics

• Breast Neoplasms (metabolism)
• Estradiol (analogs & derivatives, metabolism, pharmacology)
• Estriol (metabolism)
• Estrone (analogs & derivatives, metabolism)
• Female
• Humans
• Menstruation
• Polyunsaturated Alkamides
• Progesterone (pharmacology)
• Receptors, Progesterone (metabolism)
• Tamoxifen (pharmacology)
• Tumor Cells, Cultured