title: Nuclear translocation of β-catenin correlates with CD44 upregulation in Helicobacter pylori-infected gastric carcinoma.
abstract: Infection with Helicobacter pylori CagA-positive strains is associated with gastric adenocarcinoma. CagA H. pylori activates the β-catenin signal by translocation into nucleus which promotes carcinogenesis. Deregulated accumulation of nuclear β-catenin enhances transcription of β-catenin target genes including CD44 and promotes malignant transformation. The aim of this study was to investigate whether nuclear translocation of β-catenin correlates with CD44 expression in CagA H. pylori-infected gastric carcinoma. To address these issues, we examined 140 gastric biopsy specimens by using immunohistochemical and immunofluorescence staining, Western blot, and mutational analysis of the exon 3 β-catenin gene. The nuclear localization of β-catenin was significantly (χ(2) = 21.175; P < 0.001) increased in advanced gastric carcinoma and also correlated (χ(2) = 22.857; P < 0.001) with the CagA H. pylori positive specimens. We also observed that tyrosine-phosphorylated β-catenin was significantly (χ(2) = 14.207; P < 0.001) increased in samples showing nuclear localization of β-catenin and also it correlated (χ(2) = 43.69; P < 0.03) with the CagA H. pylori positive specimens. Exon 3 β-catenin gene mutation was not detected in H. pylori-infected gastric carcinoma. CD44 up regulation was significantly associated with tyrosine-phosphorylated β-catenin (χ(2) = 22.5; P < 0.001), and this change was closely associated with nuclear translocation of β-catenin (χ(2) = 13.393; P < 0.001) in CagA H. pylori-infected gastric carcinoma. In conclusion, our data suggest that CagA H. pylori infection is responsible for the tyrosine phosphorylation of β-catenin and its nuclear translocation, which upregulates β-catenin target gene CD44 in gastric carcinoma.
authors.affiliation: Department of Zoology, Unit of Biochemistry, University of Madras, Guindy campus, Chennai 600 025, India.
authors.forename: Gopal
authors.initials: G
authors.lastname: Udhayakumar
authors.forename: Venkatraman
authors.initials: V
authors.lastname: Jayanthi
authors.forename: Niranjali
authors.initials: N
authors.lastname: Devaraj
authors.forename: Halagowder
authors.initials: H
authors.lastname: Devaraj
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D002471:Cell Transformation, Neoplastic; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D021381:Protein Transport; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology*; D015533:Transcriptional Activation; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D018960:Hyaluronan Receptors; D051176:beta Catenin