Molecular cloning of gene sequences that are regulated by insulin-like growth factor I

Insulin-like growth factor I (IGF I) regulates the expression of a select few genes in quiescent BALB/c-3T3 cells. This was demonstrated by gel electrophoresis of radiolabeled proteins and by molecular cloning of twelve distinct IGF I-regulated cDNAs. Together, the electrophoretic and cloning data show that IGF I stimulates the expression of about 0.15% of the genes expressed by 3T3 cells, perhaps 30 genes in total. The genes encode both cytoplasmic and nuclear proteins. At the regulatory level the IGF I-controlled genes segregate into two categories. Category I genes (the minority) respond preferentially to IGF I. Their induction is prevented by actinomycin D, and they are superinduced by the combination of IGF I and anisomycin. Category II genes (the majority) respond to platelet-derived growth factor as well as to IGF I. The response of category II genes to IGF I is insensitive to actinomycin D. The data indicate that category II genes are constitutively transcribed and that IGF I regulates stability of the transcripts. The expression of category II genes correlates well with the ability of 3T3 cells to survive in serum-free culture medium.