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.
References
Nunez M, Aedo A-R, Landgren B-M, Cezan SZ, Diczfalusy E: Studies of the pattern of circulating steroids in the normal menstrual cycle. Acta Endocr (Kbh) 86: 621–633, 1977
Roberts KD, Rochefort JG, Bleau G, Chapdelaine A: Plasma estrone sulfate levels in postmenopausal women. Steroids 35: 179–187, 1980
Bradlow HL, Rosenfeld RS, Kream J, Fleisher M, O'Connor J, Schwartz MK: Steroid hormone accumulation in human breast cyst fluid. Cancer Res 41: 105–107, 1981
Raju U, Noumoff J, Levitz M, Bradlow HL, Breed CN: On the occurence and transport of estriol-3-sulfate in human breast cyst fluid. The metabolic disposition of blood estriol-3-sulfate in normal women. J Clin Endocrinol Metab 53: 847–851, 1981
Hawkins RA, Thomson ML, Killen E: Oestrone sulphate, adipose tissue, and breast cancer. Breast Cancer Res Treat 6: 75–87, 1985
Santner SJ, Feil PD, Santen RJ: In situ estrogen production via estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway. J Clin Endocrinol Metab 59: 29–33, 1984
Prost O, Turrel MO, Dahan N, Craveur C, Adessi G: Estrone and dehydroepiandrosterone sulfatase activities and plasma estrone sulfate levels in human breast carcinoma. Cancer Res 44: 661–664, 1984
Adams JB, Pewnim T, Chandra DP, Archibald L, San Foo M: A correlation between estrogen sulfotransferase levels and estrogen receptor status in human primary breast carcinoma. Cancer Res 39: 5124–5126, 1979
Sumida C, Pasqualini JR: Determination of cytosol and nuclear estradiol-binding sites in fetal guinea pig uterus by [3H]-estradiol exchange. Endocrinology 105: 406–413, 1979
Pasqualini JR, Nguyen B-L: Progesterone receptors in the fetal uterus and ovary of the guinea pig: evolution during fetal development and induction and stimulation in estradiol-primed animals. Endocrinology 106: 1160–1165, 1980
Burton K: A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62: 315–323, 1956
Gelly C, Sumida C, Gulino A, Pasqualini JR: Concentrations of oestradiol and oestrone in plasma, uterus, and other tissues of fetal guinea-pigs: their relationship to uptake and specific binding of [3H]-oestradiol. J Endocrinol 89: 71–77, 1981
Friederici HHR: The early response of capillaries to estrogen stimulation. Lab Invest 17: 322–333, 1967
Horwitz KB, McGuire WL: Estrogen control of progesterone receptor in human breast cancer. J Biol Chem 253: 2223–2228, 1978
Seibert K, Shafie SM, Triche TJ, Whang-Peng JJ, O'Brien SJ, Toney JH, Huff KK, Lippman ME: Clonal variation of MCF-7 breast cancer cells in vitro and in athymic nude mice. Cancer Res 43: 2223–2239, 1983
Vic P, Vignon F, Derocq D, Rochefort H: Effect of estradiol on the ultrastructure of the MCF-7 human breast cancer cells in culture. Cancer Res 42: 667–673, 1982
Pasqualini JR, Gelly C, Lecerf F: Biological effects and morphological responses to estriol, estriol-3-sulfate, estriol-17-sulfate and tamoxifen in a tamoxifen-resistant cell line (R-27) derived from MCF-7 human breast cancer cells. Eur J Cancer Clin Oncol 22: 1495–1501, 1986
Vignon R, Terqui M, Westley B, Derocq D, Rochefort H: Effects of plasma estrogen sulfates in mammary cancer cells. Endocrinology 106: 1079–1086, 1980
Wilking N, Carlström K, Gustafsson SA, Sköldefors H, Tollbom O: Oestrogen receptors and metabolism of oestrone sulphate in human mammary carcinoma. Eur J Cancer 16: 1339–1344, 1980
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pasqualini, J.R., Gelly, C. & Lecerf, F. Estrogen sulfates: Biological and ultrastructural responses and metabolism in MCF-7 human breast cancer cells. Breast Cancer Res Tr 8, 233–240 (1986). https://doi.org/10.1007/BF01807336
Issue Date:
DOI: https://doi.org/10.1007/BF01807336