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. Knock-down 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.
Liu
Haiou
H
Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong, China.
Huang
Xiaodong
X
Wang
Huimin
H
Shen
Aiguo
A
Cheng
Chun
C
D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D015735:Mifepristone / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013995:Time
D054758:A Kinase Anchor Proteins; D000199:Actins; C102361:Akap12 protein, rat; D018931:Antineoplastic Agents, Hormonal; C530106:Ccnd1 protein, rat; D018797:Cell Cycle Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D019938:Cyclin D1; D015735:Mifepristone; D003907:Dexamethasone; D019950:Mitogen-Activated Protein Kinase 1