Down-regulation of alpha 6 integrin, an anti-oncogene product, by functional cooperation of H-Ras and c-Myc

Background: The molecular basis of cooperation of H-Ras and c-Myc in regula ting cellular behaviour, such as cell adhesiveness, is still poorly underst ood. To investigate the role of H-Ras and c-Myc in cell adhesiveness, a con stitutively active H-Ras(V12) (H-RasV12) and c-Myc were stably expressed, s ingly or in combination in a haematopoietic cell line, and the expression a nd activity of cell adhesion molecules were monitored. Results: We have shown that the ectopic expression of H-Ras(V12), but not c -Myc alone, in a haematopoietic cell line, induces the activation of very l ate antigen-6 (VLA-6, alpha (6)beta (1)) integrin. Co-expression of H-Ras(V 12) and c-Myc in the same cells further resulted in the induction of expres sion of vascular cell adhesion molecule-1 (VCAM-1) and the inhibition of ex pression of alpha (6) 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 expressi on of the adhesion molecules, alpha (6) integrin and VCAM-1. Our results re present an unprecedented account of the cooperation of the oncogene product s, H-Ras and c-Myc, to inhibit expression of an anti-oncogene product, alph a (6) integrin.