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- Title
Down-regulation of α6 integrin, an anti-oncogene product, by functional cooperation of H-Ras and c-Myc.
- Authors
Fujimoto, Hiroko; Tanaka, Yoshiya; Liu, Zhao-Jun; Yagita, Hideo; Okumura, Ko; Kosugi, Atsushi; Morinobu, Akio; Umehara, Hisanori; Yamamura, Hirohei; Minami, Yasuhiro
- Abstract
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-Ras[sup V12] (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-Ras[sup V12], but not c-Myc alone, in a haematopoietic cell line, induces the activation of very late antigen-6 (VLA-6, α[sub 6]β[sub l]) integrin. Co-expression of H-Ras[sup V12] 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 α[sub 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 expression of the adhesion molecules, α[sub 6] 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, α[sub 6] integrin.
- Subjects
CYTOLOGY; INTEGRINS; TUMOR suppressor genes
- Publication
Genes to Cells, 2001, Vol 6, Issue 4, p337
- ISSN
1356-9597
- Publication type
Article
- DOI
10.1046/j.1365-2443.2001.00428.x