人肝癌细胞中新抑癌基因PTEN突变及其功能改变的研究

The PTEN gene (also called MMAC1/TEP1) is a tumor suppressor gene on human chromosome 10q23.3. Germline PTEN mutations are present in glioblastoma, prostate and breast cancer, and also in a wide range of human cancers. PTEN encodes the motif of dual-specifity phosphotase. PTEN mutations in tumors may result in the marked decrease in PTEN phosphotase activity, and contribute to abnormal proliferation of cells.PCR-SSCP analysis reaveled that PTEN mutated in 4 of 34 human hepatocellular carcinomas. We examined the expression of PTEN transcripts by Northern blotting and PTEN protein by Western blotting. The data showed that a bulk of human hepatocellular carcinoma tissue and two cell lines showed relatively low expression levels of PTEN mRNA and protein. PTEN expression plasmid was transfected into the hepatoma cell line SMMC-7721. It was observed that overexpression of PTEN gene significantly inhibited cell motility on extracellular matrix ( Fn ). The data showed that the overexpression of PTEN did not affect FAK expression but resulted in a decrease in FAK tyrosine phosphorylation. The level of FAK phosphorylation was inversely correlated with the level of PTEN protein. The present data also showed that overexpression of PTEN could induce apoptosis and G1 arrest in PTEN-null HEK293 cells through inhibiting PKB/Akt and MAPK phosphrylation stimulated by PDGF.

近年抑癌基因缺失和突变与细胞恶性行为特别是聚焦黏附异常受到关注。本项目研究新发现的具有磷酸酶活性的抑癌基因PTEN在人肝癌中缺失和突变即此突变与黏着斑激酶，PKB磷酸胶拖赴じ健⑶窒形哪谠诠叵担教忠职┗蛲槐涠韵赴じ椒肿咏榈嫉男藕糯嫉挠跋欤佣沂救烁伟┫赴蠵TEN突变所引起的功能改变。