The 3D Structure Altertion Of P53 Protein And Its Role In Carcinogenesis And Progression Of Osteosarcoma

Objective:Our study was to detect the mutant p53 gene and the change of P53 protein 3D structure in osteosarcoma and their relation with the immunohistochemical quantitative expression of P53,P63 and p73, aim at analyze the clinicopathologic significance of osteosarcoma and explore the mechanism of carcinogenesis and progression.Methods:Immunohistochemistry, computerized image, PCR-SSCP, DNA sequencing, computerized three-dimensional protein-modeling, reconstitute P53 3D structure, related software analysis, were used to analysis to investigate osteosarcoma.Results: 1 .The difference in those cases with p53 gene mutation located in P53 DNA binding orwith widely divergent P53 DNA binding and those cases with p53 gene mutationlocated beyond P53 DNA binding were significant in histologicalgrade(P<0.05),tumor size and metastatic (P<0.01).2.The expression level of P53, P63, P73 protein in osteosarcoma was higher than that innormal bone tissues(P<0.01). 3.Expression of P53, P63 and P73 in clinicopathological stage I was significantly lowerthan those in clinicopathological stage II, III(P<0.05). 4A significant positive correlation can be identified between P63 and P53 proteinexpression, also between P73 and P53 protein expression. (r=0.328,0.346,P<0.05). Conclusions:1. The change of the 3D structure of p53 protein have an important effect on thecarcinogenesis and progression of osteosarcoma.2.The P53 gene mutation site in osteosarcoma was mostly in GC sequence of exon, especially in exon 7, which was different with other tumors.3, Immunohistochemical expression of P63 and P73 protein was strongly associated with the change of the 3D structure of p53 protein in osteosarcoma.4. Overpression of P53, P63 and P73 may invole in the carcinogenesis and the progression of osteosarcoma,and were correlated to the degree of osterosarcoma.