Regulation of the insulin-like growth factor-I receptor gene by oncogenes and antioncogenes: implications in human cancer.

The insulin-like growth factor-I receptor (IGF-I-R) has a central role in normal cellular proliferation as well as in transformation processes. Transcription of the IGF-I receptor gene is controlled by a number of tumor suppressors, including WT1, p53, and BRCA1. It has been demonstrated that, in their wild-type form, these transcription factors can suppress the activity of the IGF-I-R promoter, with ensuing reduction in the levels of cell-surface IGF binding. On the other hand, a number of oncogenes, including mutant p53 and c-myb, and the fusion protein EWS-WT1 significantly stimulate promoter activity. Interactions between stimulatory and inhibitory transcription factors may determine the level of expression of the IGF-I-R gene and, consequently, the proliferative status of the cell.