Study of the PTEN gene expression and FAK phosphorylation in human hepatocarcinoma tissues and cell lines.
The tumor suppressor PTEN gene maps to chromosome 10q23.3 and encodes a dual specificity phosphatase. Mutations of this gene had been found in a variety of human tumors. In the present study, we analyzed the structure and expression of the PTEN gene in 34 hepatocellular carcinoma tissues and two hepatoma cell lines. We found neither homozygous nor hemizygous deletions in these samples. We, however, found point mutations in 4 of the 34 tissue samples. Five of ten hepatocellular carcinoma tissues showed reduced PTEN expression at mRNA level. HepG2 and SMMC-7721 hepatoma cells showed decreased PTEN expression at both mRNA and protein levels compared with immortalized L02 hepatic cells. PTEN mRNA in SMMC-7721 hepatoma cells could be reduced by TGF-betaI treatment. We also found that the phosphorylation levels of FAK in both of the hepatoma cell lines were higher than that in L02 hepatic cells. Transient expression of the PTEN gene in SMMC-7721 and HepG2 hepatoma cells resulted in decreased FAK phosphorylation. The level of FAK tyrosine phosphorylation appeared to be inversely correlated with the level of the PTEN protein. In summary, our results indicated that the function of the PTEN gene in hepatocarcinomas may be impaired mainly through point mutations and expression deficiency and that the defect of PTEN in tumor cells could alter the phosphorylation of FAK.
Zhang
Lineng
L
Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, PR China.
Yu
Qiang
Q
He
Jianyu
J
Zha
Xiliang
X
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D010766:Phosphorylation; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D025521:Tumor Suppressor Proteins; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human