Interaction of MUC1 with beta-catenin modulates the Wnt target gene cyclinD1 in H. pylori-induced gastric cancer.

摘要

Beta-catenin can function as an oncogene when it is translocated to the nucleus, binds to T-cell factor (TCF) or lymphoid enhance factor and transactivate its target gene. The mechanism responsible for the activation of Wnt signaling pathway in the Cytotoxin-associated antigen A (CagA) Helicobacter pylori (H. pylori)-infected gastric carcinoma has not been elucidated. We hypothesize that whether interaction of MUC1 with beta-catenin modulates the Wnt signaling and its target gene cyclinD1 in CagA H. pylori-infected gastric carcinoma. The result demonstrate that binding of MUC1 CT with Protein Kinase C delta (PKC delta), tyrosine phosphorylation of MUC1 CT, and CagA are strongly associated with the interaction of MUC1 with beta-catenin in CagA H. pylori-infected gastric carcinoma. A statistically significant difference (chi(2) = 24.49; P < 0.001) was found when the binding of MUC1 CT and beta-catenin was compared to subcellular localization of beta-catenin. We also observed significant statistical correlation (chi(2) = 14.885; P < 0.001) between the cyclinD1 overexpression and the subcellular localization of beta-catenin. The overexpression of cyclinD1 was significantly higher (chi(2) = 13.785; P < 0.002) in advanced gastric carcinoma with CagA H. pylori infection. In addition cyclinD1 overexpression was significantly higher (chi(2) = 37.267; P < 0.001) with the interaction of MUC1 CT with beta-catenin in advanced gastric cancer. These findings indicate that MUC1 CT plays a role in the intracellular signaling through its interaction with beta-catenin and upregulate the Wnt target gene cyclinD1 in CagA H. pylori-infected gastric carcinoma.