Down-regulation of alpha6 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 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, 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.


CONCLUSIONS
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.
Fujimoto
H
H
Department of Biomedical Regulation & Parasitology, Kobe University, School of Medicine, Kobe, Japan.
Tanaka
Y
Y
Liu
Z J
ZJ
Yagita
H
H
Okumura
K
K
Kosugi
A
A
Morinobu
A
A
Umehara
H
H
Yamamura
H
H
Minami
Y
Y
D000818:Animals; D015152:Blotting, Northern; D002448:Cell Adhesion; D002460:Cell Line; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D039121:Integrin alpha6beta1; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D017931:DNA Primers; D039121:Integrin alpha6beta1; D016023:Integrins; D007797:Laminin; D016271:Proto-Oncogene Proteins c-myc; D017474:Receptors, Laminin; D019010:Vascular Cell Adhesion Molecule-1; D016283:Proto-Oncogene Proteins p21(ras)