The anti-proliferation mechanism of glucocorticoid mediated by glucocorticoid receptor-regulating gene expression.
Glucocorticoid (GC) hormones exert an antiproliferative effect on various cells. The effect is mainly mediated by glucocorticoid receptor (GR) which acts as a transcription factor. Ligand-bound GR translocates from the cytoplasm into the nucleus to modulate gene expression in a variety of ways. Although the framework of transcriptional regulation by the GC/GR has been described, the molecular mechanism of antiproliferative effect of GC is still largely unclear. In this article, we reviewed GC-induced changes in gene expression that are involved in GC-antiproliferative effect, and mainly focused on our recently identified glucocorticoid-responsive genes, TGF-beta receptor type II (TbetaRII) and small GTP binding protein RhoB. We found that expressions of TbetaRII and RhoB were up-regulated by ligand-bound GR at mRNA and protein levels. Blocking the effect of TbetaRII by TbetaRII neutralizing antibody or reduction of RhoB mRNA expression by RNAi diminished dexamethasone-inhibitory effect on cell proliferation, thus confirming that these genes are involved in GC anti-proliferation effect. Collectively, GC up-regulating the expressions of RhoB and TbetaRII play an important role in GC anti-proliferation effect.
Lu
Jian
J
Department of Pathophysiology, the Second Military Medical University, Shanghai, 200433, PR China.