Interaction of MUC1 with beta-catenin modulates the Wnt target gene cyclinD1 in H. pylori-induced gastric cancer.
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.
Udhayakumar
Gopal
G
Department of Zoology, Unit of Biochemistry, University of Madras, Guindy Campus, Chennai, India.
Jayanthi
Venkatraman
V
Devaraj
Niranjali
N
Devaraj
Halagowder
H
D000230:Adenocarcinoma / Q000235:genetics / Q000382:microbiology; D000328:Adult; D000942:Antigens, Bacterial / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016481:Helicobacter Infections / Q000150:complications / Q000378:metabolism; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000382:microbiology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C060192:MUC1 protein, human; D018396:Mucin-1; D051153:Wnt Proteins; D051176:beta Catenin; C080866:cagA protein, Helicobacter pylori; D019938:Cyclin D1