Source:http://linkedlifedata.com/resource/pubmed/id/15547725
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2004-11-19
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pubmed:abstractText |
Hepatocellular carcinoma (HCC) is one of the most common malignancies in Southeast Asia. Hyperphosphorylation of retinoblastoma (pRB) by cyclin/CDKs in G1/S transition is required for its inactivation and cell cycle progression. In the present study, we report that phosphorylation of pRB at Ser780 and Ser795 was detected in 71% (33 of 46) and 63% (29 of 46) of HCCs examined respectively. pRB protein was undetectable in 13% (6 of 46) of HCCs examined. Phosphorylated pRB was localized in the nuclei of hepatocarcinoma cells. Benign hepatocytes exhibited very weakly or no nuclear staining for phosphorylated pRB. Over-expression of E2F-1, cyclin D1, Cdk-2, Cdk-4 and cyclin A was found in 64% (30 of 46), 43% (26 of 46), 28% (11 of 46), 71% (33 of 46) and 63% (29 of 46) of HCCs examined respectively and this was correlated with elevation of ERK. Treatment of HepG2 cells with MEK1/2 inhibitor U0126 resulted in cell cycle arrest, downregulation of cyclin D1 and Cdk-2 expression and inhibition of pRB phosphorylation at Ser780 and Ser795. Ectopic expression of activated MEK1 in HepG2 cells increased cyclin D1 and Cdk-2 expression, phosphorylation of pRB at Ser780 and Ser795, and percentage of cells in S phase. Our data indicate that activated ERK plays an important role in cyclin D1 and Cdk-2 expression and phosphorylation of pRB at Ser780 and Ser795 in liver cancer cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin D1,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1019-6439
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1839-47
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15547725-CDC2-CDC28 Kinases,
pubmed-meshheading:15547725-Carcinoma, Hepatocellular,
pubmed-meshheading:15547725-Cyclin D1,
pubmed-meshheading:15547725-Cyclin-Dependent Kinase 2,
pubmed-meshheading:15547725-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:15547725-Humans,
pubmed-meshheading:15547725-Liver Neoplasms,
pubmed-meshheading:15547725-Phosphorylation,
pubmed-meshheading:15547725-Retinoblastoma Protein,
pubmed-meshheading:15547725-Tumor Cells, Cultured
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pubmed:year |
2004
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pubmed:articleTitle |
Extracellular signal-regulated kinase induces cyclin D1 and Cdk-2 expression and phosphorylation of retinoblastoma in hepatocellular carcinoma.
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pubmed:affiliation |
Laboratory of Molecular Endocrinology, Division of Cellular and Molecular Research, National Cancer Centre of Singapore, 169610, Singapore. cmrhth@nccs.com.sg
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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