title: Efficient induction of apoptosis by wee1 kinase inhibition in hepatocellular carcinoma cells.
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.
authors: Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors: Tomomi
authors: T
authors: Kogiso
authors: Aoyama hospital, Tokyo Women's Medical University, Tokyo, Japan.
authors: Hikaru
authors: H
authors: Nagahara
authors: Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors: Etsuko
authors: E
authors: Hashimoto
authors: Institute of Gastroenterology, Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan.
authors: Shunichi
authors: S
authors: Ariizumi
authors: Institute of Gastroenterology, Department of Surgery, Tokyo Women's Medical University, Tokyo, Japan.
authors: Masakazu
authors: M
authors: Yamamoto
authors: Institute of Gastroenterology, Department of Internal Medicine, Tokyo Women's Medical University, Tokyo, Japan.
authors: Keiko
authors: K
authors: Shiratori
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D053773:Transforming Growth Factor beta1; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases