Pasqualini J R, Gelly C, Nguyen B L
C.N.R.S. Steroid Hormone Research Unit, Foundation for Hormone Research, Paris, France.
Ann N Y Acad Sci. 1990;595:106-16. doi: 10.1111/j.1749-6632.1990.tb34286.x.
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.
不同的雌激素 - 3 - 硫酸盐（硫酸雌酮、硫酸雌二醇和硫酸雌三醇）可在不同的乳腺癌细胞系中引发重要的生物学反应；孕激素受体显著增加。然而，硫酸雌酮 - 17 - 硫酸盐未观察到显著作用。硫酸雌酮 - 3 - 硫酸盐产生生物学反应的原因是这些硫酸盐被水解，而这些细胞系中不存在针对C17 - 硫酸盐的硫酸酯酶活性。在不同的激素依赖性乳腺癌细胞系（MCF - 7、R - 27和T47D）中，[3H] - 硫酸雌酮有很高比例转化为雌二醇（E2），但在激素非依赖性乳腺癌细胞系（MDA - MB - 231和MDA - MB - 436）中发现很少或没有转化。不同的抗雌激素药物（他莫昔芬及其衍生物）以及另一种强效抗雌激素ICI 164,384，在将硫酸雌酮与不同的激素依赖性乳腺癌细胞系孵育后，可显著降低雌二醇浓度。在激素非依赖性乳腺癌细胞系中，未观察到对硫酸雌酮摄取和转化的显著影响。数据表明，在激素非依赖性细胞系中，硫酸雌酮的硫酸酯酶活性非常低；然而，对MCF - 7和MDA - MB - 436细胞匀浆后进行的比较动力学研究表明，硫酸酯酶活性相似，这表明在激素依赖性和激素非依赖性细胞系中，硫酸雌酮水解的机制不同。在用[3H] - 硫酸雌酮与MCF - 7细胞系孵育后，孕激素也会显著降低摄取和雌二醇水平。结论是，硫酸雌激素在乳腺癌雌激素的生物学反应中可发挥重要作用，并且控制硫酸酯酶和17 - 羟基类固醇脱氢酶的活性是乳腺癌细胞系中雌二醇浓度和能力的关键步骤。
