Dexamethasone inhibits proliferation and stimulates SSeCKS expression in C6 rat glioma cell line

Although there is ample evidence that dexamethasone (DEX) has an antiproliferative effect on C6 glioma cells, the molecular mechanism remains elusive. Src suppressed C kinase substrates (SSeCKS), as a member of PKC substrates, have been implicated to be a negative regulator of cell proliferation. in this study, we provided novel evidence that DEX induced the expression of SSeCKS mRNA and protein in a time- and dose-dependent manner, and translocation of SSeCKS from the cytosol to the membrane. The glucocorticoid receptor antagonist, RU486, significantly decreased DEX-induced SSeCKS expression, inhibited SSeCKS translocation and actin cytoskeleton reorganization after DEX challenge. Knockdown of SSeCKS expression by RNA interference inhibited DEX-induced actin cytoskeleton reorganization and reversed DEX-induced growth arrest. We also presented the novel observation that knock-down of SSeCKS expression elevated the expression of cyclin D1 and the phosphorylation of extracellular signal-regulated Kinase 1/2, indicating that SSeCKS is involved in the regulation of cell cycle related proteins and is essential for DEX induced growth arrest. (C) 2009 Elsevier B.V. All rights reserved.