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.
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