Down-regulation of alpha6 integrin, an anti-oncogene product, by functional cooperation of H-Ras and c-Myc

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
H FujimotoY Minami

Abstract

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. 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, alpha6beta1) 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 alpha6 integrin, a candidate anti-oncogene product, leading to a loss of adhesiveness to laminin (Lm), a ligand for VLA-6. Cooperation of H-Ras and c-Myc reciprocally regulates expression of the adhesion molecules, alpha6 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, alpha6 integrin.

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Citations

Jun 27, 2002·Seminars in Cancer Biology·Manuel PatarroyoIsmo Virtanen
Oct 23, 2003·Nature Reviews. Molecular Cell Biology·Kayoko KinbaraMark H Ginsberg
Jan 24, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Donald MassaroLinda Biadasz Clerch

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