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The Loss Of Expression And Significance Of PTEN In Hepatocelluar Carcinoma And The Effects Of PTEN Gene Transfer In Cell Line HHCC

Posted on:2002-07-15Degree:MasterType:Thesis
Country:ChinaCandidate:T WangFull Text:PDF
GTID:2144360032952370Subject:Surgery
Abstract/Summary:PDF Full Text Request
Hepatocellular carcinoma(HCC) is one of the most common neoplasm in China, its morbidity ranks the third and the death rate ranks the second among all kinds of neoplasm. Increasing genetic evidence exists that carcinogenesis must be understood in terms of accumulation of mutation in regulatory genes, including activation of oncogenes and inactivation or loss of tumor suppressor genes. Now, the gene transfer has been paid more attention to because of the bad therapeutic efficacyPTEN is a tumor suppressor gene identified on human chromosome 10q23 3 that is frequently mutated or deleted in multiple advanced cancers, which is first discovered by three independent research groups It can inhibit the genesis, proliferation, invasion and metastasis of carcinoma cells.The purpose of this study is to investigate the relationship between the loss of expression of PTEN and the HCC development and malignancy, to investigate the effects of PTEN gene transfer in human hepatocelluar carcinoma Cell Line HHCC.We employed Streptavidin Biotin peroxidase Complex (SABC) methods. Monoclonal antibody against PTEN protein on archival HCC materials. Then use cationic liposome LipofectAmine2000 to delivery retrovirus vector pBabe-PTEN-PURO which contains PTEN and pBabe-PURO into PTEN-deficient HCC cell line HHCC respectively to study cell growth, adhesion, apoptosis, cell cycle, ultrastructure alteration in Vitro and nude mice tumorgenesis ability in Vivo.?-Results PTEN protein was detected in 19 out of 63 cases of HCC, much higher than that of normal liver tissues and cirrhotic liver tissues The negative rate has a statistical significant relationship with the difference, metastasis and prognosis. After PTEN was transfected into HHCC and expressed, cells growth rate obviously slows down and adhesion rate drops. FCM shows a little apoptosis peak and an obvious Gl block in cell cycle, EMS shows cells lose some malignant features in ultrastructure and nude mice tumorgenesis ability in Vivo is weakened.Conclusion: (1): loss of tumor suppressor PTEN protein expression usually occurs in HHCC pathologic progression and is correlated with differentiation, metastasis and prognosis This protein may help the identification of HCC's pathologic grade and predict the prognosis. (2) PTEN can inhibit HHCC growth, adhesion in Vitro and tumorgenesis ability in Vivo obviously. It may play a role in liver cancer gene therapy...
Keywords/Search Tags:Tumor Suppressor Gene, PTEN, Hepatocellular carcinoma, HHCC, Immunohistochemistry, gene transfer
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