Actions of a progestogen on human breast cancer cells: mechanisms of growth stimulation and inhibition.
Medroxyprogesterone acetate (MPA) reduced the proliferation of MCF-7 cells with a maximal response at 100 nM. A subline ('M' cells) resistant to this action remained responsive to antioestrogen but showed a poor response to dexamethasone (DEX). Experiments with mixtures of MPA and DEX showed that MPA acts on wild-type MCF-7 cells through a glucocorticoid as well as a progestogen mechanism. The growth of 'M' cells was stimulated by MPA at 100 nM or greater and the drug increased polyamine concentrations in 'wild-type' as well as 'M' cells. It is suggested that both progestogen and glucocorticoid receptors may mediate the effects of high-dose MPA therapy in breast cancer. The possible stimulation of the growth of some cell types by MPA requires further investigation.
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D017258:Medroxyprogesterone Acetate; D011073:Polyamines / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism
D000970:Antineoplastic Agents; D011073:Polyamines; D011987:Receptors, Steroid; D004958:Estradiol; D003907:Dexamethasone; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone