Regulation of growth hormone and epidermal growth factor receptors by progestins in breast cancer cells.
A 24 hr incubation of T-47D human breast cancer cells with R5020, a synthetic progestin, resulted in a 200-250% increase in the specific binding of human growth hormone (hGH) and epidermal growth factor (EGF) by these cells. This effect was specific for progestins in that similar responses were observed with progesterone, medroxyprogesterone acetate and ORG 2058 but no significant increases in hGH or EGF binding were observed in cells incubated with testosterone, estradiol or hydrocortisone. Increased binding was due to an increase in the concentration of receptors (hGH, control = 6,490 +/- 500, progestin treated = 13,180 +/- 3,270 sites/cell; EGF, control = 33,380 +/- 7,410, progestin treated = 67,460 +/- 20,330 sites/cell) while the affinity constants for the hormone-receptor interactions were unchanged by progestin treatment. The specific binding of insulin, calcitonin, transferrin and concanavalin A was unaffected by these treatments. It is concluded that expression of hGH and EGF receptors in this breast cancer cell line is regulated by progestins.
D001943:Breast Neoplasms / Q000378:metabolism*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D011282:Pregnenediones / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011372:Progestins / Q000494:pharmacology*; D011397:Promegestone / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011986:Receptors, Somatotropin
D011282:Pregnenediones; D011372:Progestins; D011956:Receptors, Cell Surface; D011986:Receptors, Somatotropin; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; D011374:Progesterone; D004815:Epidermal Growth Factor; D013006:Growth Hormone; D011397:Promegestone; D017258:Medroxyprogesterone Acetate; D066246:ErbB Receptors; D008525:Medroxyprogesterone