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

Y. Shimizu, N. Yamamichi, K. Saitoh, A. Watanabe, T. Ito, M. Yamamichi-Nishina, M. Mizutani, Naohisa Yahagi, T. Suzuki, C. Sasakawa, S. Yasugi, M. Ichinose, H. Iba

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)884-893
Number of pages10
JournalOncogene
Volume22
Issue number6
DOIs
Publication statusPublished - 2003 Feb 13
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Stomach
Epithelial Cells
Rous sarcoma virus
Epithelium
Mesoderm
Avian Stomach
Oncogenes
Proventriculus
Anoikis
Gene Transfer Techniques
Electroporation
MAP Kinase Signaling System
Organ Culture Techniques
Mitogen-Activated Protein Kinase Kinases
Retroviridae
Collagen Type I
Fibronectins
Sarcoma
Genetic Recombination

Keywords

  • Apoptosis
  • Epithelial-mesenchymal transition
  • MAP kinase
  • RSV
  • V-src

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Shimizu, Y., Yamamichi, N., Saitoh, K., Watanabe, A., Ito, T., Yamamichi-Nishina, M., ... Iba, H. (2003). Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach. Oncogene, 22(6), 884-893. https://doi.org/10.1038/sj.onc.1206174

Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach. / Shimizu, Y.; Yamamichi, N.; Saitoh, K.; Watanabe, A.; Ito, T.; Yamamichi-Nishina, M.; Mizutani, M.; Yahagi, Naohisa; Suzuki, T.; Sasakawa, C.; Yasugi, S.; Ichinose, M.; Iba, H.

In: Oncogene, Vol. 22, No. 6, 13.02.2003, p. 884-893.

Research output: Contribution to journalArticle

Shimizu, Y, Yamamichi, N, Saitoh, K, Watanabe, A, Ito, T, Yamamichi-Nishina, M, Mizutani, M, Yahagi, N, Suzuki, T, Sasakawa, C, Yasugi, S, Ichinose, M & Iba, H 2003, 'Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach', Oncogene, vol. 22, no. 6, pp. 884-893. https://doi.org/10.1038/sj.onc.1206174
Shimizu Y, Yamamichi N, Saitoh K, Watanabe A, Ito T, Yamamichi-Nishina M et al. Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach. Oncogene. 2003 Feb 13;22(6):884-893. https://doi.org/10.1038/sj.onc.1206174
Shimizu, Y. ; Yamamichi, N. ; Saitoh, K. ; Watanabe, A. ; Ito, T. ; Yamamichi-Nishina, M. ; Mizutani, M. ; Yahagi, Naohisa ; Suzuki, T. ; Sasakawa, C. ; Yasugi, S. ; Ichinose, M. ; Iba, H. / Kinetics of v-src-induced epithelial-mesenchymal transition in developing glandular stomach. In: Oncogene. 2003 ; Vol. 22, No. 6. pp. 884-893.
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