The Expression Of HMGB1,TopBP1 In Bladder Cancer And Clinical Study

The generation and development, of tumor is a complicated mechanism. Manyresearch dedicated the biological behavior of tumor are the result ofchange in single or multitude gene. The activation of oncogene anddeactivation of antioncoge contribute to the change from normal cellsto cancer cells. The study of molecular genetics of tumor not onlycontribute to the diagnosis and prediction of prognosis, but also showus more clearly the pathogenesy of tumor. Though the study of moleculargenetics of tumor is just in initial phase, it already give us someinspiration. The generation and development of bladder cancer are theresult of change of cell molecular biology. Nowadays the focus of theresearch is the differentially-expressed genes between normal bladdercell and transitiomal cell carcinoma, the mechanism ofdifferentially-expressed genes, the correlation of differentially-expressed genes with clinical stage, pathological grade, recurrence andprognosis.The study aims to search for the differentially-expressed genes betweenbetween normal bladder cell and transitiomal cell carcinoma, and thento find out the relationship between these genes and biological behaviourof bladder cancer. During former study, we combined the technique of LCM,RNA Amplification,DDRT-PCR to get 50 differentially-expressed genes.This study we pick out 6 binds for further research.Section one: The study of genic differential expression between bladder cancer cells and bladder transitional cellsObjective: Identify differentially-expressed genes. Methods: (1))Clo ne and sequence the bands or differentially-expressed genes; (2)Homology searches are performed against Genebank entries using NCBI BLASTprograms; (3)Detect the relative intensity of expression of differentially-expressed genes by Quantitative real-time PCR. Results: (1) Named the differentially-expressed genes fragments BC1-6; (2) Results ofHomology searches against Genebank: some fragments were homologousto known genes; the others to uncharacterized human clones on chromosomes; (3)The authenticity of differences of genic expression was 100% validated by Quantitative real-time PCR. Conclusion: (1)DeterminedHMGB1, TopBP1as the correlative gene with bladder cancer at genelevel. (2)Deduce BC2,3,4,5 may be the new correlative gene with bladde-r cancer or cancer.Section two: The study of protein expression of HMGB1, TopBP1 in bladder cancerObjective: (1)Detect whether corresponding protein expression differences of HMGB1,TopBP1 exists or not, and then make sure that the twoprotein associate with bladder cancer. (2) Detect the correlation among two protein with pathological grade and invasive depth, and thento find out whether the two proteins take part in the generation anddevelopment of bladder cancer. Methods: Applying immunohistochemistryin tissue microarray, detect the protein expression of HMGB1, TopBP1in bladder cancer(respective 30cases of pathological gradeâ… ,â…¡,â…¢)and bladder transitional cells(30cases), and analyse the correlationbetween the protein expressions and pathological grade or invasive deptb. Result: (1) The protein expression of HMGB1 is up-regulated incancer cells, moreover negatively correlated with pathological grade, positively correlated with invasive depth. (2) The protein expression of TopBP1 is down-regulated in cancer cells; No significant differenoes of TopBP1 expression were found between pathological grade, invasive depth. Conclusion: (1) At both of gene and protein level determined HMGB1 as an oncogene correlative with bladder cancer. (2)At both of gene and protein level determined TopBP1 as a tumor suppressorgene correlative with tumor or/and bladder cancer...