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Activation of ErbB3–PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas

Oncogene volume 22, pages 1294–1301 (2003)Cite this article

Abstract

Signet-ring cell carcinomas are malignant dedifferentiated carcinomas, which are frequently found in the stomach. We previously demonstrated that a 200 kDa protein is often constitutively phosphorylated on tyrosine and bound to phosphatidylinositol 3-kinase (PI3-kinase) in signet-ring cell carcinoma cells. In this study, we purified the 200 kDa protein from an extract of NUGC-4 cells, a cell line of signet-ring cell carcinoma, and identified it as ErbB3. ErbB3 was found to be phosphorylated selectively in dedifferentiated adenocarcinoma cell lines among various gastric cancer cell lines. Expression of a constitutively active chimeric receptor consisting of ErbB2 and ErbB3 in HCC2998 cells, a highly differentiated adenocarcinoma cell line, revealed that the signaling triggered by phosphorylation of ErbB3 was important for dedifferentiated phenotypes such as loss of cell–cell interaction and high expression of MUC1/DF3 antigen, a marker of the malignant tumors. Taken together, activation of ErbB3 pathway may contribute to the development of dedifferentiated carcinomas.

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Acknowledgements

We sincerely thank Dr Seisuke Hattori for a critical reading of the manuscript. This work was supported by a Grant in Aid for Cancer Research from the Ministry of Education, Science, Sports, and Culture of Japan.

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Author notes

  1. Michimoto Kobayashi

    Present address: Division of Cellular Proteomics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

Authors and Affiliations

  1. Department of Applied Biological Chemistry, Laboratory of Biological Chemistry, Faculty of Agricultural and Life Science, University of Tokyo, Yayoi 1-1-1, Bunkyo-ku, Tokyo, 113-8657, Japan

    Michimoto Kobayashi, Sayoko Ihara & Yasuhisa Fukui

  2. Central Laboratories for Key Technology, Kirin Brewery Company Ltd, Yokohama, 236-0004, Kanagawa, Japan

    Akihiro Iwamatsu & Azusa Shinohara-Kanda

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  1. Michimoto Kobayashi
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  5. Yasuhisa Fukui
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Correspondence to Yasuhisa Fukui.

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Kobayashi, M., Iwamatsu, A., Shinohara-Kanda, A. et al. Activation of ErbB3–PI3-kinase pathway is correlated with malignant phenotypes of adenocarcinomas. Oncogene 22, 1294–1301 (2003). https://doi.org/10.1038/sj.onc.1206256

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