title: Effect of the progestagen R5020 (promegestone) and of progesterone on the uptake and on the transformation of estrone sulfate in the MCF-7 and T-47d human mammary cancer cells: correlation with progesterone receptor levels.
abstract: In the present study we have explored the actions of the progestagen R5020 (Promegestone: 17 alpha, 21-dimethyl-19-nor-pregna-4, 9-diene-3,20-dione) and progesterone on the uptake of [3H]estrone sulfate ([3H]E1S) and its conversion to estradiol (E2) by two hormone-dependent mammary cancer cell lines: MCF-7 and T-47D. R5020 or progesterone significantly decreased the uptake of [3H]E1 and its conversion to (E2). In the cells of the two lines, R5020 or progesterone (5 x 10(-6) M) decreased the E2 concentrations by 2-3 times in relation to the levels in untreated cells. E1S (1 x 10(-7) M) also increased expression of the progesterone receptor (PR) and both R5020 (5 x 10(-6) M) and progesterone (5 x 10(-6) M) blocked this stimulatory action of E1S in cells of both cell lines. As E2 is one of the main factors of cancerization in the breast and estrone sulfate is quantitatively the most important precursor of E2 in this tissue, the decrease of E2 by these progestagens could open new possibilities for the control of E2 in the breast cancer tissue.
authors.affiliation: C.N.R.S. Steroid Hormone Research Unit, Foundation for Hormone Research, Paris, France.
authors.forename: J R
authors.initials: JR
authors.lastname: Pasqualini
authors.forename: C
authors.initials: C
authors.lastname: Varin
authors.forename: B L
authors.initials: BL
authors.lastname: Nguyen
mesh_terms: D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D004958:Estradiol / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D011374:Progesterone / Q000494:pharmacology*; D011397:Promegestone / Q000494:pharmacology*; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D011980:Receptors, Progesterone; D014316:Tritium; D004970:Estrone; D011374:Progesterone; D004958:Estradiol; D011397:Promegestone; C017296:estrone sulfate