The insulin-like growth factor-I receptor as an oncogene

The insulin-like growth factor-I receptor (IGF-IR) mediates the biological actions of both IGF-I and IGF-II. The IGF-IR is expressed in most transformed cells, where it displays potent antiapoptotic, cell-survival, and transforming activities. IGF-IR expression is a fundamental prerequisite for the acquisition of a malignant phenotype, as suggested by the finding that IGF-IR-null cells (derived from IGF-IR knock-out embryos) are unable to undergo transformation when exposed to cellular or viral oncogenes. This review article will focus on the underlying molecular mechanisms that are responsible for the normal, physiological control of IGF-IR gene expression, as well as the cellular pathways that underlie its aberrant expression in cancer. Examples from the clinics will be presented, including a description of how the IGF system is involved in breast, prostate, pediatric, and gynecological cancers. Finally, current attempts to target the IGF-IR as a therapeutic approach will be described.