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Interaction of MUC1 with β‐catenin modulates the Wnt target Gene cyclinD1 in H . pylori ‐induced gastric cancer
Author(s) -
Udhayakumar Gopal,
Jayanthi Venkatraman,
Devaraj Niranjali,
Devaraj Halagowder
Publication year - 2007
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20311
Subject(s) - caga , biology , wnt signaling pathway , muc1 , cancer research , catenin , helicobacter pylori , tyrosine phosphorylation , cancer , oncogene , beta catenin , signal transduction , microbiology and biotechnology , gene , cell cycle , biochemistry , genetics , virulence
Abstract β‐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 β‐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 δ (PKC δ), tyrosine phosphorylation of MUC1 CT, and CagA are strongly associated with the interaction of MUC1 with β‐catenin in CagA H. pylori ‐infected gastric carcinoma. A statistically significant difference ( χ 2 = 24.49; P < 0.001) was found when the binding of MUC1 CT and β‐catenin was compared to subcellular localization of β‐catenin. We also observed significant statistical correlation ( χ 2 = 14.885; P < 0.001) between the cyclinD1 overexpression and the subcellular localization of β‐catenin. The overexpression of cyclinD1 was significantly higher ( χ 2 = 13.785; P < 0.002) in advanced gastric carcinoma with CagA H. pylori infection. In addition cyclinD1 overexpression was significantly higher ( χ 2 = 37.267; P < 0.001) with the interaction of MUC1 CT with β‐catenin in advanced gastric cancer. These findings indicate that MUC1 CT plays a role in the intracellular signaling through its interaction with β‐catenin and upregulate the Wnt target gene cyclinD1 in CagA H. pylori ‐infected gastric carcinoma. © 2007 Wiley‐Liss, Inc.