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Selective G2/M arrest in a p53(Val135)-transformed cell line induced by lithium is mediated through an intricate network of MAPK and β-catenin signaling pathways.
MedLine Citation:
PMID:  22884810     Owner:  NLM     Status:  Publisher    
AIMS: Lithium is a common mood stabilizer to treat bipolar disorder. It has a narrow window of therapeutic action and its mechanism of action and possible side effects are still not fully understood. Lithium is a potent inhibitor of glycogen synthase kinase 3β (GSK-3β). Previous studies indicated that lithium can induce cell cycle arrest by stabilization of p53. In order to further elucidate the signaling mechanism of lithium-induced cell cycle arrest and its potential pharmacological effect on p53 transformed cell lines, we studied the effect of lithium on the rat fibroblast cell line R6 and a p53(Val135) transformed cell line R6T2 (hereafter referred to as T2). MAIN METHODS: We monitored the effects of lithium on cell cycle progression by FACS analysis and the activation of MAPK signaling pathways by Western blot using anti-phospho-MAPK antibodies in R6 and T2. KEY FINDINGS: We report here lithium can induce G2/M arrest in T2 independent of β-catenin signals. Lithium increases phosphorylation of extracellular signal-regulated kinases (ERKs) leading to the up-regulation of p53 levels and subsequent G2/M arrest. Lithium also induced phosphorylation of p38 MAPK, consequently downregulated p53 and alleviated G2/M cell cycle arrest. We further showed the gate-keeping role of p53 in the lithium-induced G2/M arrest in the T2 cell line. SIGNIFICANCE: Our results reveal a novel mechanism underlying the differential response of the transformed and normal R6 to lithium-induced G2/M cell cycle arrest and delineate the multiplicity of signaling pathways dictating the cell fate in responding to cell stress signals.
Man Kin Marco Tsui; William Chi Shing Tai; Wing Yan Wong; Wen Luan Wendy Hsiao
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-1
Journal Detail:
Title:  Life sciences     Volume:  -     ISSN:  1879-0631     ISO Abbreviation:  Life Sci.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
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