RRC ID 45137
Author Kogiso T, Nagahara H, Hashimoto E, Ariizumi S, Yamamoto M, Shiratori K.
Title Efficient induction of apoptosis by wee1 kinase inhibition in hepatocellular carcinoma cells.
Journal PLoS ONE
Abstract Transforming growth factor-β1 (TGF-β1) potently inhibits human hepatocellular carcinoma (HCC) cell growth. Here we demonstrated that TGF-β1-induced apoptosis is mediated by decreased phosphorylation of cdc2 at Tyr15 accompanied by down-regulation of Wee1 kinase expression. As expected from these results, a Wee1 kinase inhibitor efficiently induced apoptosis in HCC cells in the absence of TGF-β1 treatment. In surgically resected samples, Wee1 kinase was expressed in moderately to poorly differentiated HCC, whereas no Wee1 kinase expression was observed in non-cancerous tissue, including cirrhotic tissue. Our results suggest that Wee1 kinase inhibitors may be a practical novel therapeutic option against advanced HCC.
Volume 9(6)
Pages e100495
Published 2014
DOI 10.1371/journal.pone.0100495
PII PONE-D-14-17661
PMID 24960176
PMC PMC4069002
MeSH Apoptosis / drug effects* CDC2 Protein Kinase Carcinoma, Hepatocellular / genetics Carcinoma, Hepatocellular / metabolism* Cell Cycle Proteins / antagonists & inhibitors* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Line, Tumor Cyclin-Dependent Kinases / metabolism Enzyme Activation / drug effects Gene Expression Humans Immunohistochemistry Liver Neoplasms / genetics Liver Neoplasms / metabolism* Nuclear Proteins / antagonists & inhibitors* Nuclear Proteins / genetics Nuclear Proteins / metabolism Protein Kinase Inhibitors / pharmacology* Protein-Tyrosine Kinases / antagonists & inhibitors* Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / metabolism RNA Interference Transforming Growth Factor beta1 / pharmacology
IF 2.776
Times Cited 3
Human and Animal Cells