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Altered Expression and Localization of Connexin32 in Human and Murine Gastric Carcinogenesis

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Abstract

Background

Intercellular communication via gap junctions, composed of protein subunits called connexins (Cxs), plays a key role in controlling cell growth, differentiation and carcinogenesis. Impaired gap junctional intercellular communication has been reported in various cancers and diseases.

Aims

We investigated Cx32 expression patterns and semiquantitatively assessed Cx32 expression in cancers and preneoplastic lesions. To determine if cell proliferation is correlated with Cx32 expression, we evaluated Ki67 expression in a gastric cancer mouse model.

Methods

In human and mouse, normal stomach and gastric adenocarcinoma tissues were used for immunohistochemical analyses.

Results

Cx32 was detected at cell–cell (intercellular) contact points in normal cells and exhibited punctate intercellular and intracytoplasmic staining in cancer cells. The frequency of Cx32 loss of expression was significantly higher in human adenocarcinomas than in normal stomach. As tumor cells were less differentiated, Cx32 expression levels and intercellular and intracytoplasmic staining were also significantly lower. The Cx32 expression pattern in the mouse gastric cancer model was similar in several important respects to that of human. In mucous metaplasia of the mouse stomach, Cx32 was mainly expressed in the cytoplasm of epithelial cells. There was also an inverse correlation between Cx32 expression and cell proliferation in mouse tumors. However, there was no difference in the levels of Cx32 mRNA between normal and cancerous tissues.

Conclusions

These findings suggest that altered Cx32 expression, a loss of intercellular Cx32 and a gain of intracytoplasmic Cx32 in the form of punctate “dot”, plays an important role in the formation of gastric adenocarcinomas.

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Acknowledgments

This work was supported by Brain Korea 21 Project. This study was partially supported by the Research Institute for Veterinary Science, Seoul National University.

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Authors and Affiliations

  1. Laboratory of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Korea

    Hyang Jee & Dae-Yong Kim

  2. Vanderbilt University School of Medicine, Nashville, TN, 37232-2733, USA

    Ki Taek Nam

  3. Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Korea

    Hyo-Jung Kwon

  4. Genomic Research Center for Gastroenterology, Ajou University School of Medicine, Suwon, Korea

    Sang-Uk Han

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  1. Hyang Jee
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  2. Ki Taek Nam
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Correspondence to Dae-Yong Kim.

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Jee, H., Nam, K.T., Kwon, HJ. et al. Altered Expression and Localization of Connexin32 in Human and Murine Gastric Carcinogenesis. Dig Dis Sci 56, 1323–1332 (2011). https://doi.org/10.1007/s10620-010-1467-z

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  • DOI: https://doi.org/10.1007/s10620-010-1467-z

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