Estrogen sulfates: Biological and ultrastructural responses and metabolism in MCF-7 human breast cancer cells

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Abstract
The biological effects and ultrastructural alterations by different estrogen-3-sulfates (E1-3-S and E2-3-S) and estradiol-17-sulfate (E2-17-S) were studied in the MCF-7 mammary cancer cell line in culture. The estrogen-3-sulfates very significantly stimulated the progesterone receptor (PR). The values (in pmoles/mg DNA ± SE) were: control, 0.46 ± 0.09; E1-3-S, 2.24 ± 0.30, and E2-3-S, 2.56 ± 0.45. The value of PR after E2-17-S incubation (0.56 ± 0.24) was similar to the non-treated cells. The PR values obtained by the incubation of unconjugated estrone and estradiol were: 2.63 ± 0.45 and 2.27 ± 0.36, respectively. Analysis of the unconjugated estrogens in the medium indicated significant hydrolysis of estrogen-3-sulfates but not of E2-17-S. Using [3H]-E1-3-S, an important transformation was observed inside the cells, a great part being converted to estradiol (>60% in the nuclear fraction). Electron microscopic examination indicated alterations in the secretory system after incubation with estrogen-3-sulfates similar to those obtained with unconjugated estradiol. The effect provoked by E2-17-S was significantly less than for the other sulfates. As estrogen sulfates are quantitatively the most important form of estrogens in the mammary gland, it is suggested that estrogen-3-sulfates play an important role in the biological responses to estrogens in breast cancer.