Rat Glioblastoma Cells Expressing an Antisense RNA to the Insulin-like Growth Factor-1 (IGF-1) Receptor Are Nontumorigenic and Induce Regression of Wild-Type Tumors

摘要: Insulin-like growth factor-1 (IGF-1) and IGF-2 are critical regulators of cell proliferation. The growth-promoting action both ligands is mediated by the type 1 IGF receptor (IGF-1R). We have investigated role IGF-1R in tumorigenicity rat C6 glioblastoma cells. For this purpose, antisense RNA to was introduced into cells either addition oligodeoxynucleotides or transfection with plasmids that express RNA. At low density, grew slowly serum-free medium proliferated sole IGF-1 IGF-2. Both stable a plasmid expressing an inhibited IGF-1-mediated monolayers clonogenicity soft agar. Sense sense-expressing had no effect on parameter. In transfectants, tyrosine-phosphorylated receptors were not detectable, although they easily detected wild-type When injected s.c. syngeneic immunocompetent rats, tumors developed within week. contrast, stably transfected overexpressing nontumorigenic. Moreover, when injected, subsequent tumor formation completely prevented. Finally, injection rats carrying established caused complete regression tumors. results demonstrate importance growth, clonogenicity, tumorigenicity. Although mechanism presently unknown, fact leads already suggests possibility practical applications.