Tumor Suppressor Gene P33 ~ (ing1) Expression And Mutation In Colorectal Cancer Study

The foremost protective mechanisms against oncogenesis and progression of cancer are the tumor suppressor genes. So long as these genes are fully active, they serve as potent buffers against tumor progression. Up to now, the best known and maybe the most important of all tumor suppressor genes is P53, which is altered in about half of all human tumors, making it the most frequent target for genetic alterations in cancer. According to Garkavtsev's report, P53 does not restrain cancer single-handedly and seems to require an intimate partner-a novel candidate tumor suppressor, p33INGI p33INGi has been implicated in the negative regulation of cell proliferation and in the control of apoptosis and cellular aging. Conversely, if production of p33ING1 is down-regulated or suppressed by using antisense mRNA, cells can escape from P53-mediated growth inhibition. Recent studies also indicate that p331NGi also cooperates with p53 for induction of apoptosis in the p53-restraint glioma. The biological effects of p331NG1 imply that its functional loss might contribute to tumorgenesis. But reports on alteration of p33INGI in human cancer is scarce. The expression of p331NG1 p53 P2lWatI proteins were investigated with immunohistochemical SP method in 52 patients with colorectal carcinoma and the adjacent normal mucosa. We also detected the expression of p33No and INGIL mRNA with RT-PCR and screened its mutation by means of PCR- SSCP in the same samples. Furthermore, the relationship between the expression of these genes and the clinopathologic features was determined. The aim of this study was to explore the possible roles 0fp331N3l and INGIL in the tumorgenesis and development of colorectal cancer and to investigate the possibility of these genes as a putative gene-therapeutic strategy or a prognosis indicator. The main results and conclusions: 1. Both the mRNA and protein of p33INGI were extensively expressed in normal colorectal mucosae. The protein locates in the nuclei of the epithelium cells especially at the crest rather than at the recess, indicating the involvement 0fp33lNGI in the aging of the epithelium cells. 2. The significant decreased expression of p33ING1 mRNA and negative immunostainning of its protein were observed in 57.7% and 51.9% colorectal carcinomar tissues respectivly in comparision with that of normal rnucosae. An impaired expression of this gene was associated with a worse Duke's stage and metastasis of lymph nodes, but showed no correlation with other clinopathologic features. 3. Mutation rate of p33INGI was low in colorectal carcinoma. The infrequent mutation and impaired expression of p33INGI indicated that p33INGI attributed to the late events of tumorgenesis and progression in colorectal cancer through down-regulating its expression rather than through mutation. 4. There was a significant decrease of p33INGI mRNA and protein in tumors that negative for P53 immunostaining, possibly responsible for the inactivity of wtP53 in some of the patients with colorectal cancer. 5. The expression of pJ3INGI protein were correlated positively to that of P2lwaa, which further indicating involvement of p33INGI in the modulation of the expression of P21 wafl 6. The expression of p33INGI mRNA and protein was obviously positive...