Metabolism and biologic response of estrogen sulfates in hormone-dependent and hormone-independent mammary cancer cell lines. Effect of antiestrogens.
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.
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
D001943:Breast Neoplasms / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004964:Estriol / Q000378:metabolism* / Q000031:analogs & derivatives; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism; D005260:Female; D006801:Humans; D008598:Menstruation; D053284:Polyunsaturated Alkamides; D011374:Progesterone / Q000494:pharmacology; D011980:Receptors, Progesterone / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D053284:Polyunsaturated Alkamides; D011980:Receptors, Progesterone; D013629:Tamoxifen; C031555:estradiol sulfate; D004970:Estrone; C027974:estriol 3-sulfate; D011374:Progesterone; D004958:Estradiol; C051781:ICI 164384; D004964:Estriol; C017296:estrone sulfate