Actions of a progestogen on human breast cancer cells: mechanisms of growth stimulation and inhibition

Abstract

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.