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 journalArticlepeer-review

11 Scopus citations


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 (US)
Pages (from-to)337-343
Number of pages7
JournalGenes to Cells
Issue number4
StatePublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology


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