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Expression And Functional Implications Of Tumor Suppressor Gene PTEN In Colorectal Cancer

Posted on:2003-11-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:G B ZhengFull Text:PDF
GTID:1104360092465036Subject:Surgery
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Colorectal cancer is one of the most common and malignant tumor in our country. Although great progress has been made in treatment of colorectal cancer , the really cause of colorectal cancer is unclear, and the effect of Colorectal cancer treatment is still unsatisfactory with the limits of surgical resection, radiotherapy, chemotherapy . Therefore, It is urgent to put more efforts to do further research for the molecular carcinogenesis mechanism and to find out the ideal target gene which controls tumor cells proliferation and migration, and which can acts precisely as a parameter to predict the prognosis or metastasis of the tumor. Just like other tumors, the development of colorectal cancer is a complex process involving many genes and factors. The phosphorylation level of protein tyrosine, precisely regulated by PTKs and PTPs, may play an important role in the cellular signal transduction and cell cycle progression. As many PTKs are encoded by pro-oncogenes, it has been postulated thatsome of PTPs may act as tumor suppressor gene for a long time. But this assumption is not testified until the discovery of PTEN tumor suppressor gene.Studding on the mechanism of tumor suppressor gene has been becoming a hot spot in the field of medicine since the first suppress gene Rb was discovered in 1986.PTEN,as a newly-found tumor suppressor gene, was immediately attracted much attention from scientist in different countries and designed as a second "star molecule" subsequent to p53 since characterized and cloned respectively by Jing Li, Peter A. Steck and DaMing Li. In 1997. PTEN has been found to be inactivated by point mutations or homozygous deletions in many malignant tumors such as glioblastoma, prostate carcinoma, breast carcinoma and Cowden`s disease. Although much work has been done on the relationships between PTEN gene and some tumors such as endometrial carcinoma, glioblastoma, prostate carcinoma, breast carcinoma and melanoma and so on, there are few reports on the relationship between the expression of PTEN and Colorectal cancer. Using Northern Blot, Western Blot, Immuno-histochemistry and gene transfection, we screened a panel of human colorectal cancer tissues with respect at the PTEN mRNA and protein expression levels to investigate the exact role of PTEN in the development of colorectal cancer It was shown that the average value of PTEN mRNA in colorectalcancer were lower than that in paired para-carcinoma tissues (p<0.05). The low mRNA expression level of the 5.5 kb transcript were significantly associated with serum CEA value, tumor grade ,and clinical stage(p <0.05). However no significant relationship was found with age, tumor size, and histological pattern(p>0.05). The low mRNA expression levels of the 4.4 kb and 2.4kb transcript were significantly associated with serum CEA value, tumor grade, clinical stage and histological pattern(p <0.05). no significant relationship was detected with age, tumor size, and other pathological parameters.(p>0.05). The low mRNA expression level of the 1.8 kb transcript in Colorectal cancer was significantly associated with clinical stage only (p<0.05).The low expression level of PTEN protein was significantly associated with serum CEA value and clinical stage (lymphoid or other organs metastasis)(p<0.05). However no significant relationship was found with age, tumor size, tumor grade, clinical stage, and histological pattern(p >0.05).After transfecting PTEN gene into LOVO cell stably, we found that invasion potency of LOVO cell decreased significantly And also PTEN may decrease the adhesive ability of LOVO to specific extracellular substrate through specific receptors on cell surface.By using western blot assay, we found that the level of PTEN protein in colorectal cancer cell line HT-29can be significantly upgradedby chemotherapeutic drugs(5-FU,MMC,DDP) in clinically relevent concentration.Our results suggest that expression of PTNE may be involved in the development of Colorectal cancer, that expression of...
Keywords/Search Tags:Colorectal Carcinoma, Tumor Suppressor Gene, Gene Expression
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