Mediation of glucocorticoid receptor function by transforming growth factor beta I expression in human PC‐3 prostate cancer cells

Abstract

Abstract We investigated the role of glucocorticoids in controlling the proliferation of androgen‐independent PC‐3 human prostate cancer cells via the action of transforming growth factor beta 1 (TGF β1). The presence of glucocorticoid receptor (GR) in PC‐3 cells was detected by immunoblotting analysis using a rabbit anti‐GR polyclonal antibody against the synthetic human GR peptide (hGR 383–393 ). In PC‐3 cells, GR bound radiolabeled dexamethasone with an affinity similar to wild‐type GR. In addition, GR‐ligand complex bound radiolabeled DNA as detected by DNA band‐shift analysis on gel electrophoresis and trans ‐activated the mouse mammary tumor virus‐thymidine kinase‐chloramphenicol acetyltransferase chimeric gene in transiently transfected PC‐3 cells. Dexamethasone (0.1 up to 100 nM) and TGF β1 (0.5 up to 50 ng/ml) inhibited PC‐3 cell proliferation. TGF β1 and dexamethasone both increased the distribution of PC‐3 cells into the G 1 /G 0 phase of the cell cycle. Platelet‐derived growth factor (PDGF) stimulated the proliferation of PC‐3 cells and overcame dexamethasone's inhibition of PC‐3 cell growth. Dexamethasone's inhibition (10 –7 M) of PC‐3 cell growth was completely neutralized by RU 486 (10 –6 M) and partly neutralized by anti‐TGF β1 polyclonal antibody. Furthermore, dexamethasone up modulated the expression of TGF β1 mRNA in PC‐3 cells. Because dexamethasone's inhibition was neutralized at least in part by an anti‐TGF β1 polyclonal antibody and dexamethasone up modulated the expression of TGF β1 mRNA in PC‐3 cells, we conclude that GR function in human PC‐3 prostate cancer cells is mediated at least in part by TGF β1 expression.