The Role Of β-catenin, CyclinD1, Smad4 In Pancreatic Carcinomas

Pancreatic carcinoma is one of the gastrointestinal malignancies. The prognosis is poor because of its rapid progress, low rate resecting and most cases are discovered at the late stage. Although many researchers studied pancreatic cancer a lot,the mechanism of tumorigenesis is not very clear yet. It has been demonstrated that the activation of oncogene, the inactivation of tumor suppress gene and the aberrance of the cell cycle regulation ,all these may lead to pancreatic cancer. Recently, the researchers had focused on the signaling pathways' crosstalk. Several studies have shown that cooperation between transforming growth factor (TGF-8) and Wnt signaling pathway play a role in tumorigenesis. 6-catenin is required for cell-cell adhesion. 6-catenin mediates cell adhesion through interactions with E-cadherin, and at the same time, it is a regulator of the Wnt pathway. Wnt signaling allows 8-cat to accumulate in the cytoplasm and subsequently translocate to the nucleus and at where 8-cat activates the target genes, CyclinD1. It pushes cell cycle from G1 phase to S phase increasing cell proliferation. As a tumor suppress gene of pancreas, Smad4 is a necessary regulator in TGF-6 pathway . The mutation of Smad4 leads to the disruption of TGF-6 pathway so that promotes the development of the cancer. In order to investigate the possible mechanism of pancreatic carcinogenesis and provide something helpful for diagnosis and therapy, an immunohistichemical technique was used to detect the expression of 8-catenin, CyclinDl, Smad4 in normal pancreatic tissues, benign diseases and cancer of pancreas. Material and methods:1. 14 normal pancreatic tissues confirmed pathologically which were adjacent to the tumor, 10 benign pancreatic disease and 37 primary pancreatic ductal adenocarcinoma tissues were collected. Each case has detailed information.2. SABC immunohistochemical technique was used to detect the expression of B-catenin, CyclinDl, Smad4 in these three kinds of tissues.3. SPSS10.0 statistical software was used to analyze the date. Using Fisher's exact probabilities analyzed the correlation between G-catenin, CyclinDl, Smad4 and clincopathological features of tumors. Spearman rank correlation was used to analyze the relationship among three protein .A difference was considered significant if P value was less than 0.05.Results1. In normal pancreatic tissues the staining of B-catenin was located on the cell membrance , but in the pancreatic cancer the membrance staining decreased and mainly located in the cytoplasm or nucleus. The abnormal expression was 67.57 %( 25/37) in pancreatic cancer, only 40 %( 4/10) cases were detected abnormal staining in benign disease; none of the staining in normal pancreas was abnormal. There were significant differences among them (P<0.05). In pancreatic cancer, the abnormal expression rate of I / II stages (47.06%) was lower than that of III/IV stages (85% )(P<0.05). The abnormal expression of the B-catenin in cancer tissues with lymph node metastasis (85%,17/23) was significantly higher than the ones with no metastasis (47.06%,8/17) (P<0.05).But it had no relationship with pathological differentiation grade(P>0.05)2. Positive staining of CyclinDl was mainly located in the nucleus. 26 cases of pancreatic cancer and 3 cases of benign disease were detected positive staining; there was no positive expression in normal pancreas. There were significant differences between cancer and benign, normal tissues (P<0.05). No significant differences were found between the expression of CyclinDl and the differentiation, clinical stage and lymph node metastasis (P>0.05).3. The expression of Smad4 was observed in the cytoplasm and nucleus. The expressionrate (51.35%, 19/37) of pancreatic cancer was lower than that of the normal pancreas (92.85. %, 13/14) and benign disease (90%, 9/10) (P<0.05). Smad4 expression had no relationship with the clinical parameters of pancreatic cancer. (P>0.05).4. The expression of 6-catenin and CyclinDl were both positive in 21 ca...