Effects of Plasma Estrogen Sulfates in Mammary Cancer Cells*

Abstract

The ability of estrogen conjugates to act as estrogen precursors in mammary tumor cells has been examined. One hour after injection of [3H]estradiol to ovariectomized C3H mice, 50–70% of the radioactivity in mammary tumor cytosol was due to estrogen conjugates (mostly sulfate) which were probably of plasma origin. Both the C3H independent mouse mammary tumors and the ovarian dependent tumors of the 9,10-dimethyl- 1,2-benzanthracene-treated rats took up and hydrolyzed [3H]- estrone sulfate in vitro. Similarly, in the MCF7 human breast cancer cell line, estrone sulfate entered the cells and was metabolized, yielding unconjugated estrone and estradiol which were finally bound to nuclear estrogen receptor. In addition, estrone-3-sulfate and estradiol-3-sulfate were found to be active on MCF7 cells in inducing secreted proteins of 46,000 and 160,000 mol wt which are induced by a 10-fold lower concentration of unconjugated estrone and estradiol. We conclude that estrogen sulfates can act in vitro as estrogen precursors in human breast cancer cells containing sulfatases and we propose to consider their possible role in vivo as estrogen precursors. The relative resistance of estrogen conjugates to charcoal adsorption lead to overestimation of estrogen receptor sites by the charcoal assay. The conjugates may also alter the evaluation of estradiol action in cell culture, since the routine charcoal treatment of serum which is efficient in adsorbing the nonconjugated steroid is shown to be inefficient in depriving the serum from estrogen sulfates. We therefore propose that the control cells cultured with steroidfree serum can be stimulated by the estrogens liberated from the estrogen sulfates of the serum if their concentration is sufficient. (Endocrinology106: 1079, 1980)