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Kinetics of v-src-induced epithelial–mesenchymal transition in developing glandular stomach

Oncogene volume 22, pages 884–893 (2003)Cite this article

Abstract

The oncogene function in primary epithelial cells is largely unclear. Recombination organ cultures in combination with the stable and transient gene transfer techniques by retrovirus and electroporation, respectively, enable us to transfer oncogenes specifically into primary epithelial cells of the developing avian glandular stomach (proventriculus). In this system, the epithelium and mesenchyme are mutually dependent on each other for their growth and differentiation. We report here that either stable or transient expression of v-src in the epithelium causes budding and migration of epithelial cells into mesenchyme. In response to the transient expression of v-Src or a constitutive active mutant of MEK, we observed immediate downregulation of the Sonic hedgehog gene and subsequent elimination of E-cadherine expression in migrating cells, suggesting the involvement of MAP kinase signaling pathway in these processes. v-src-expressing cells that were retained in the epithelium underwent apoptosis (anoikis) and detached from the culture. Continuous expression of v-src by, for example, Rous sarcoma virus (RSV) was required for the epithelial cells to acquire the ability to express type I collagen and fibronectin genes (mesenchymal markers), and finally to establish the epithelial–mesenchymal transition. These observations would partly explain why RSV does not apparently cause carcinoma formation, but induces sarcomas exclusively.

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Acknowledgements

Monoclonal antibodies (7D6, B3/D6 and QCPN) were kindly supplied from the Developmental Studies Hybridoma Bank, IA, USA. We are grateful to Dr T Kameda for preparing the virus vector encoding GFP. We thank Dr T Yoshida and Dr T Kameda for critically reading this manuscript. We thank Ms N Hashimoto and Ms K Takeda for their assistance in preparing this manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture, Japan.

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Author notes

  1. Y Shimizu

    Present address: Second Department of Internal Medicine, Wakayama Medical College, 811-1 Kimiidera, Wakayama, 640-0012, Japan

Authors and Affiliations

  1. Division of Host–Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Y Shimizu, N Yamamichi, K Saitoh, A Watanabe, T Ito, M Yamamichi-Nishina & H Iba

  2. Division of Bacterial Infection, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    T Suzuki & C Sasakawa

  3. Laboratory Animal Research Station, Nippon Institute for Biological Science, 3331, Kamisasao, Kobuchizawa, 408-0041, Yamanashi, Japan

    M Mizutani

  4. Department of Gastroenterology, Faculty of Internal Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    N Yahagi

  5. Department of Biology, Faculty of Science, Tokyo Metropolitan University, 1-1 Minamiohsawa, Hachioji, Tokyo, 192-0397, Japan

    S Yasugi

  6. Second Department of Internal medicine, Wakayama Medical College, 811-1 Kimiidera, Wakayama, 640-0012, Japan

    M Ichinose

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  1. Y Shimizu
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Correspondence to H Iba.

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Shimizu, Y., Yamamichi, N., Saitoh, K. et al. Kinetics of v-src-induced epithelial–mesenchymal transition in developing glandular stomach. Oncogene 22, 884–893 (2003). https://doi.org/10.1038/sj.onc.1206174

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