Down-regulation of α6 integrin, an anti-oncogene product, by functional cooperation of H-Ras and c-Myc

Hiroko Fujimoto, Yoshiya Tanaka, Zhao-Jun Liu, Hideo Yagita, Ko Okumura, Atsushi Kosugi, Akio Morinobu, Hisanori Umehara, Hirohei Yamamura, Yasuhiro Minami

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Background: The molecular basis of cooperation of H-Ras and c-Myc in regulating cellular behaviour, such as cell adhesiveness, is still poorly understood. To investigate the role of H-Ras and c-Myc in cell adhesiveness, a constitutively active H-RasV12 (H-RasV12) and c-Myc were stably expressed, singly or in combination in a haematopoietic cell line, and the expression and activity of cell adhesion molecules were monitored. Results: We have shown that the ectopic expression of H-RasV12, but not c-Myc alone, in a haematopoietic cell line, induces the activation of very late antigen-6 (VLA-6, α6β1) integrin. Co-expression of H-RasV12 and c-Myc in the same cells further resulted in the induction of expression of vascular cell adhesion molecule-1 (VCAM-1) and the inhibition of expression of α6 integrin, a candidate anti-oncogene product, leading to a loss of adhesiveness to laminin (Lm), a ligand for VLA-6. Conclusions: Cooperation of H-Ras and c-Myc reciprocally regulates expression of the adhesion molecules, α6 integrin and VCAM-1. Our results represent an unprecedented account of the cooperation of the oncogene products, H-Ras and c-Myc, to inhibit expression of an anti-oncogene product, α6 integrin.

Original languageEnglish
Pages (from-to)337-343
Number of pages7
JournalGenes to Cells
Volume6
Issue number4
DOIs
StatePublished - May 15 2001
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Fujimoto, H., Tanaka, Y., Liu, Z-J., Yagita, H., Okumura, K., Kosugi, A., Morinobu, A., Umehara, H., Yamamura, H., & Minami, Y. (2001). Down-regulation of α6 integrin, an anti-oncogene product, by functional cooperation of H-Ras and c-Myc. Genes to Cells, 6(4), 337-343. https://doi.org/10.1046/j.1365-2443.2001.00428.x