Failure of the bovine papillomavirus to transform mouse embryo fibroblasts with a targeted disruption of the insulin-like growth factor I receptor genes.
Mouse embryo cells with a targeted disruption of the insulin-like growth factor I receptor (IGF-IR) genes (R- cells) are refractory to transformation by the simian virus 40 large T antigen and/or an activated and overexpressed Ras, both of which readily transform cells from wild-type littermate embryos and other 3T3-like cells. R- cells are also refractory to transformation induced by overexpressed epidermal growth factor receptor and platelet-derived growth factor receptor beta. Since the platelet-derived growth factor receptor beta is required for transformation by bovine papillomavirus, we inquired whether the IGF-IR was also required for transformation by bovine papillomavirus E5 oncoprotein. We show here that R- cells are refractory to transformation by E5; reintroduction into R- cells of a human IGF-IR restores the susceptibility to transformation.
Morrione
A
A
Jefferson Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
DeAngelis
T
T
Baserga
R
R
D000818:Animals; D015153:Blotting, Western; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D002455:Cell Division; D002472:Cell Transformation, Viral; D002999:Clone Cells; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis; D014162:Transfection
D011994:Recombinant Proteins; D017526:Receptor, IGF Type 1