| Bladdr cancer is the most common malignant tumor of urinary tract, the formation and development of tumors are always Followed by the activation of oncogenes and inactivation of Anti-oncogenes , which are the two kinds of changes interacted with but different from each other . Many have associations with the information and development of bladder cancer among the anti-oncogens that have been found to be connected with cell canceration of Human such as Rb, WTI , P53 , MCC , P16 , NFI and APC et al. 1, Rb geneRb gene ( retinoblastoma anti-oncogene ) code Rb protein of 110 ku (pRb). The pRb pathway can provide Gl/S check-point control , that is : growth factors such as PDGF , EGF and IL-2 combined with their receptors and accelerate the expression of cyclin genes . the complex of cyclins and their receptorsphosphorylate Rb , the phosphorylated Rb then releases the proteins combined with and inhibited by it such as transcriptor E2F family and C-Ab of kinase activity . The free E2F enters the nuclear and combine with a series of specific promoter regions such as promoter regions of genes c-myc, b-myb, cdc2 , TK and E2F-1 , and promote the expression of these genes ; the product of such genes help the cell pass the check-point and get into the cell cycle . CKI can prevent Rb to be phosphorylated by inhibition of the cyclins-CDKs kinase activity , the Rb not phosphorylated can complex with E2F to block the transcription activity of E2F. During that control pathway, the P16-cyclinDl-CDK4/6-Rb-E2F approach is comparative unambiguous. Absence of the Rb protein, indicative of gene mutation, is found more frequently in tumors of high grade and stage and is clearly associated with poor outcome.2. cyclin D1Cyclins are a group proteins whose expressive level acutely alter along the cell cycle. At present, cyclins isolated from animal are chiefly devided into 8 kinds and 13 subset: A1, A2, B1, B2, B3, C, D1, D2, D3, E, F, G and H.Arises of malignant tumor is maladjustment of cell cycleactually. Different cyclins combine to corresponding cyclin dependent kinase at different period, then accelerat the completion of cell cycle. Thereinto, the role of cyclin Dl and CDK4 are more important. Cyclin Dl excess express in several kindes of tumors, such as Parathyroid adenoma, mantle cell lymphoma, skin malignant melanoma mammary cancer, lung cancer, liver cancer , esophageal carcinoma , bladder cancer and cervical cancer, and so on . Expresson of cyclin Dl in bladder transitional cell carcinoma is increased , and it' s male ratio heighten along the augment of pathology grade. 3. P16 geneP16 gene is a kind of anti-oncogene which encode 16 ku long protein(called p16); p16 also a species of cyclin dependent inhibitor (GDI), which act on CDK/CyclinD complex directly, competetively conbine to CDK4, CDK6, and then leads to the dissociation of CDK/CyclinD complexs and inhibiton of phosphorylate of Rb gene, to urge the retardarce of cell cycle, finally result in growth and differentiation of cells. Abnormally alteration of P16 gene may leads to derangement of regulation of G1 terminal restricton point of cell cycle, and anomaly proliferation occurs. Inactive mechanism of P16 gene found up to date includes at least three kinds: (1)deletion offunction and structure, cyclinu/ LUK.4 s activation boost stimulating cell' s productive splitting, at last, cellsP16 gene; (2)mutation of P16 gene; (3) methylation of 5' CpG island of P16 gene. P16 protein is inhibitor of cyclin dependent kinase4 (CDK4), which may inhibit the change-over from cell cycle G1 phase to S phase, bring on restrict of cell proliferation. When mutation of p16 gene leads to loss of it' s function and structure, cyclinD/ CDK4' s activation boost up,are uncontrolled and evolve to cancer of carcinoma.Experiments proved that variation of P16 not only relate to tumor' s occurrence but also participate in progress and relapse of tumors, Low expression of P16 protein may nearly correlate to tumor cells' s proliferation and transfer, and...
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