TY - JOUR
T1 - Down-regulation of α6 integrin, an anti-oncogene product, by functional cooperation of H-Ras and c-Myc
AU - Fujimoto, Hiroko
AU - Tanaka, Yoshiya
AU - Liu, Zhao Jun
AU - Yagita, Hideo
AU - Okumura, Ko
AU - Kosugi, Atsushi
AU - Morinobu, Akio
AU - Umehara, Hisanori
AU - Yamamura, Hirohei
AU - Minami, Yasuhiro
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=17744400712&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17744400712&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2443.2001.00428.x
DO - 10.1046/j.1365-2443.2001.00428.x
M3 - Article
C2 - 11318876
AN - SCOPUS:17744400712
VL - 6
SP - 337
EP - 343
JO - Genes to Cells
JF - Genes to Cells
SN - 1356-9597
IS - 4
ER -