查看文章

The role of the insulin receptor substrate 1 (IRS-1) in cellular transformation was studied in R- cells, which are 3T3-like fibroblasts derived from mouse embryos with a targeted disruption of the insulin-like growth factor I receptor gene. These cells cannot be transformed by oncogenes that readily transform cells originating from wild-type littermate embryos (or other 3T3-like cells). In the present study, we demonstrate that in R- cells, the overexpression of the functional IRS-1 protein was sufficient to induce a mitogenic response to insulin but did not promote transformation, as measured by colony formation in soft agar. The coexpression of IRS-1 and the SV40 T antigen, however, induced transformation. Conversely, expression of an antisense IRS-1 RNA reversed the transformed phenotype in wild-type cells carrying the T antigen. Since the type 1 insulin-like growth factor receptor, by itself, is fully transforming, we …