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Study Of The Transcriptional Expression And Mutation Of P73 Gene In Esophageal Carcinoma And Its Clinical Significance

Posted on:2003-07-31Degree:DoctorType:Dissertation
Country:ChinaCandidate:B FengFull Text:PDF
GTID:1104360092975317Subject:Surgery
Abstract/Summary:PDF Full Text Request
The esophageal cancer is one of the most common cancers in 10 kinds of carcinomas with human being. There is new 3 hundred thousands cases increased with the esophageal cancer in the world of each year. Among of these patients, about 70% cases took place in our country. Because of absent from serous membrane of the esophageal adventitia, tumour cell invaded quickly into neighboring tissues and often metastasized regional lymphoid nodule or the place of distant organs. The survival rate in the 5 years was only 10%~34% in despite of adopted surgical operation and radiation therapy or chemotherapy. The formation of esophageal cancer was a procedure of conversion form normal cell into malignity cell in long action each other by multiple factors and phases. The procedure included a series of different gene abnormality and mutation, which result in malignant changes of normal epithelium through persistent accumulation. The changes of gene included mainly two different sides: activation of primary tumor gene and loss of activation of anti-oncogene. Thus the correlative genes of esophageal cancer are investigated and explained the tumorigenesis or development of mechanism with esophageal cancer in the level of molecular biology, which can provide earlier period diagnosis and develop a new therapeutic tool for esophageal cancer. There is a certain clinical significance in the esophageal cancer.The p53 gene was one of anti-oncogenes by studied most extensively and systemically in research of tumor field, and one of the most frequently molecule event by certification in the gene abnormity of many human tumors. Themutation rate of p53 gene was about 50% in all human tumors. There was also tight correlation between the mutation of p53 and tumorigenesis or development in esophageal cancer tissues. The mutation of p53 gene was identified that it was a very early molecule abnormity event by other country's scholar in the most primary esophageal squamous cell carcinomas (ESCC). Although there were many different manners of mutation, the mutation rate of p53 gene was high to about 80% in ESCC or in esophageal adenocarcinomas (EADC). The p73, as a first new candidate anti-oncogene discovered of p53 family member in 1997 by Caput and Kaghad et al, consisted of anti-oncogene family together with p53 gene, and was special paid attention by investigator. The study had already showed that p73 gene was located at Ip36.33, centromere subterminal domain of short arm on the maps in human chromosome, which domain considered that many anti-oncogenes were located. There was 2.5Kb homological base sequence between the transcriptional production of p73 and that of p53 gene, and there were three regions of function correspondence in the level of protein between p73 gene and p53. There were six hotspots of mutation with complete correspondence between p73 and p53 in the combined regions of DNA. Their function posessed also high similarity, which all could suppress cell growth and induce cell apoptosis mainly through transcriptional activation of p21WAF-1. There was extensive expression of p73 gene with the low level in the human body. The transcriptional production of p73 gene was detected in the tissues or organs of human brain, heart, spleen and kidney et al with RT-PCR... The playing role of p73 gene was not identical in different tumour tissue. For example, because there was p73 polymorphism and loss of heterozygosity (LOH) frequently, the normal presence of p73 gene was key importance, and p73 was very important anti-oncogene in the neuroblastoma, cancer of colon, melanoma and mammary cancer et al. The mutation rate of p73 was very low level in the pulmonary carcinoma, and did not mainly playing role of restraining tumour, because it could not preventtumorigenesis or development of lung cancer. It appeared that one point at issue was predicted: as a anti-oncogene and bring into full play of action in restraining tumour, the p73 gene had a tissue specificity eategory. Up to the present, p73 function and fashion of the act...
Keywords/Search Tags:Esophageal carcinoma, p73 gene, Gene expression, Mutation, RT-PCR, Western blotting, PCR-SSCP, HMA, Immunohistochemistry
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