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Experssions Of Protein 4.1s In Colorectal Carcinoma

Posted on:2008-11-27Degree:MasterType:Thesis
Country:ChinaCandidate:W P FengFull Text:PDF
GTID:2144360215960228Subject:Cell biology
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Colorectal cancer is one of the most common and malignant tumor in our country. Just like other tumors, the development of colorectal cancer is a complex process involving many genes and factors. Although great progress has been made in treatment of colorectal cancer, the really treatment is still unsatisfactory with the limits of surgical resection, radiotherapy, chemotherapy, the mechanism underlying the pathogenesis are largely undefined. Therefore, it is urgent to put more efforts to do further research for the molecular carcinogenesis mechanism and to find out the ideal target gene which controls tumor cells proliferation and migration, and which can acts precisely as a parameter to predict the prognosis or metastasis of the tumor.The tumorigenic cause is the activation of oncogene and the deactivation of tumor suppress gene (TSG). TSG can't suppress the cell cycle, via homozygosis absence, loss of heterozygosity (LOH), point mutation, promoter region methylation or deactivation to cause malignant transformation. It's common the allelic LOH in tumor cells, analysis of LOH will provide a clue of TSG site, and help us to find unknow TSG.Protein 4.1, one of the proteins belonging to the erythrocyte membrane skeleton is a new candidate. The protein 4.1 of the red blood cell (4.1R, EPB41 encoding) is a multifunctional protein that localizes to the membrane skeleton and stabilizes erythrocyte shape and membrane mechanical properties, such as deformability and stability, via lateral interactions with spectrin. Non-elytroid cells express the 4.1R homologues: 4.1N (EPB41L1 encoding), 4.1G (EPB41L2 encoding), 4.1B (EPB41L3 encoding), and 4.1O (FRMD3 encoding), and the whole group belongs to the protein 4.1 family.This research focused on the exploration of the relationship among the expressions of protein 4.1 family members and the pathological features in colorectal carcinoma patients of our country by immunohistochemistry (IHC); and detected four Micro-satellite markers of gene EPB41L3 (4.1B) by LOH in order to provide a microbiological explanation and interpretation to the occurrence of colorectal cancer.The results of IHC showed that the expressions of 4.1s in the colorectal carcinoma tissues were obviously lower in comparison with those in the normal organization tissues (H_c= 44.700 6, H_c= 31.406 7, H_c= 13.623 3; P < 0.01) except for the 4.1G (H_c= 2.028 2, P > 0.05). The expressions of 4.1N and B in the colorectal carcinoma tissues from patients were positively correlated with cell differentiation (r_s = 0.274 67, r_s= 0.280 21; P < 0.01). The expression of 4.1R was associated with the degree of soakage (r_s= 0.032 461, P < 0.01) and the lymphatic metastasis (r_s= 0.244 40, P < 0.05). The expression of 4.1G was up-regulation with the soakage (r_s= 0.235 49, P < 0.05). There were no dependability between the expressions of 4.1s in the colorectal carcinoma tissues of patients and the age (r_s= -0.133 64, r_s= -0.056 73, r_s = 0.027 35, r_s = -0.005 39; P > 0.05). There were also no statistical meanings between the expressions of protein 4.1s and the gender of the patients (H_c= 0.055 5. H_c= 0.234 3, H_c= 0.612 2, H_c= 0.057 2; P > 0.05). The PCR test was conducted in fifteen paraffin-embedded specimens. Seven of them (46.7%) were individual information. Among these seven cases, four (26.7%) showed LOH, which is 57.1% of the individual information. They indicated: 1. There was an evident correlation between the absent or down regulation of 4.1N and 4.1B and the histological grade, which implied the absence or down regulation of 4.1N and 4.1B was an early event in colorectal carcinoma pathogenesis. 2. There was an evident correlation between the expressions of 4.1R, 4.1G and the soakage or the lymphatic metastasis of colorectal carcinoma, which implies that it concerned with the development of colorectal cancer. 3. This research showed that the LOH rate of EPB41L3 was low. We have also demonstrated that EPB41L3 LOH was not the most common mechanism of the absence or down regulation of 4.1B in sporadic colorectal carcinoma. 4. This research suggests protein 4.1 family as a new carcinoma marker. Measurement of 4.1 expression is of value in diagnose and evaluating the prognosis of colorectal carcinoma.
Keywords/Search Tags:colorectal carcinoma, protein 4.1, IHC, genetic expression, LOH
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