Modulation of lactogenic receptors by progestins in cultured human breast cancer cells.
Progesterone receptors (PgR) are present in many breast cancers, but few specific actions of progestins in breast cancer cells have been reported. We now report that progestins specifically modulate lactogenic receptor expression in cultured T-47D and MCF-7 human mammary carcinoma cells. When T-47D cells were preincubated for 24 h with 1 nM medroxyprogesterone acetate (17 alpha-acetoxy-6 alpha-methyl-4-pregnene-3,20-dione), specific binding of [125I]human GH ([125I]hGH) and [125I]human PRL was increased to 205 +/- 22% (+/- SE) (P less than 0.01) and 175 +/- 32% (P less than 0.05), respectively, of that in control cultures. There was no significant effect on cell number and no significant enhancement of specific binding of [125I]porcine insulin, [125I]salmon calcitonin, [125I]human transferrin, or [3H] Concanavalin A. Lactogenic receptor number was increased from 6,490 +/- 500 (n = 12) to 13,180 +/- 3,270 (n = 7; P less than 0.01) sites/cell, with no significant change in affinity for hGH. Progesterone, which is readily metabolized by these cells, was less potent than the synthetic progestins (medroxyprogesterone acetate, R 5020 (17 alpha, 21-dimethyl-19-norpregn-4,9-diene-3,20-dione), and ORG 2058 (16 alpha-ethyl-21-hydroxy-19-norpregn-4-en-3,20-dione), but physiological concentrations of progesterone (1 nM) significantly enhanced specific binding of [125I]hGH to 153 +/- 23% of the control value (n = 6; P less than 0.05). Physiological concentrations of androgens, estrogens, and glucocorticoids had no significant effect. MCF-7 cells were considerably less sensitive to these effects of progestins than T-47D cells, probably due to the lower PgR concentration in MCF-7 cells. These observations, which indicate that lactogenic receptor expression is controlled, at least in part, by progestins in these mammary carcinoma cell lines, may have important implications in the management of human breast cancer, where high levels of this receptor may reflect a functional PgR and a highly hormone-dependent phenotype.
D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D011372:Progestins / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018000:Receptors, Peptide; D011980:Receptors, Progesterone / Q000378:metabolism; D011986:Receptors, Somatotropin
D006728:Hormones; D011372:Progestins; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; D011980:Receptors, Progesterone; D011986:Receptors, Somatotropin; C028202:placental lactogen receptor; D004958:Estradiol; D013006:Growth Hormone; D003513:Cycloheximide; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone