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Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma

Oncogene volume 28, pages 2910–2918 (2009)Cite this article

Abstract

The partition-defective 3 (PAR-3) protein is implicated in the formation of tight junctions at epithelial cell–cell contacts. We investigated DNA copy number aberrations in human esophageal squamous cell carcinoma (ESCC) cell lines using a high-density oligonucleotide microarray and found a homozygous deletion of PARD3 (the gene encoding PAR-3). Exogenous expression of PARD3 in ESCC cells lacking this gene enhanced the recruitment of zonula occludens 1 (ZO-1), a marker of tight junctions, to sites of cell–cell contact. Conversely, knockdown of PARD3 in ESCC cells expressing this gene caused a disruption of ZO-1 localization at cell–cell borders. A copy number loss of PARD3 was observed in 15% of primary ESCC cells. Expression of PARD3 was significantly reduced in primary ESCC tumors compared with their nontumorous counterparts, and this reduced expression was associated with positive lymph node metastasis and poor differentiation. Our results suggest that deletion and reduced expression of PARD3 may be a novel mechanism that drives the progression of ESCC.

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Acknowledgements

This study was supported by Grants-in-Aid for Scientific Research (18390223 and 20590408) from the Japan Society for the Program of Science (KY).

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Authors and Affiliations

  1. Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    K Zen, K Yasui, Y Gen, O Dohi, N Wakabayashi, S Mitsufuji, Y Itoh, T Okanoue & T Yoshikawa

  2. Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

    Y Zen & Y Nakanuma

  3. Department of Molecular Hematology and Oncology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    M Taniwaki

  4. Department of Hepatology, Saiseikai Suita Hospital, Suita, Japan

    T Okanoue

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  1. K Zen
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Correspondence to K Yasui.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Zen, K., Yasui, K., Gen, Y. et al. Defective expression of polarity protein PAR-3 gene (PARD3) in esophageal squamous cell carcinoma. Oncogene 28, 2910–2918 (2009). https://doi.org/10.1038/onc.2009.148

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