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Nuclear translocation of β-catenin correlates with CD44 upregulation in Helicobacter pylori-infected gastric carcinoma

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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 (χ2 = 21.175; P < 0.001) increased in advanced gastric carcinoma and also correlated (χ2 = 22.857; P < 0.001) with the CagA H. pylori positive specimens. We also observed that tyrosine-phosphorylated β-catenin was significantly (χ2 = 14.207; P < 0.001) increased in samples showing nuclear localization of β-catenin and also it correlated (χ2 = 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 (χ2 = 22.5; P < 0.001), and this change was closely associated with nuclear translocation of β-catenin (χ2 = 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.

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Acknowledgments

The authors would like to thank Dr. Rajkumar, Dr. Revathi, and Dr. Murali for providing the gastric biopsy specimens. This study was supported by the grants from the UGC and the ICMR.

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Authors and Affiliations

  1. Department of Zoology, Unit of Biochemistry, University of Madras, Guindy campus, Chennai, 600 025, India

    Gopal Udhayakumar & Halagowder Devaraj

  2. Department of Medical Gastroenterology, Stanley Medical College, Chennai, India

    Venkatraman Jayanthi

  3. Department of Biochemistry, University of Madras, Guindy campus, Chennai, India

    Niranjali Devaraj

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  1. Gopal Udhayakumar
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  2. Venkatraman Jayanthi
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  3. Niranjali Devaraj
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Correspondence to Halagowder Devaraj.

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Udhayakumar, G., Jayanthi, V., Devaraj, N. et al. Nuclear translocation of β-catenin correlates with CD44 upregulation in Helicobacter pylori-infected gastric carcinoma. Mol Cell Biochem 357, 283–293 (2011). https://doi.org/10.1007/s11010-011-0899-x

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