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 and cell-survival activities. IGF-IR levels are tightly regulated by the concerted action of secreted (e.g. peptide and steroid hormones, growth factors and cytokines) and cellular (e.g. transcription factors, oncogenes and tumor suppressors) factors. The mode of action of many tumor suppressors involves transcriptional suppression of the IGF-IR gene, with a subsequent reduction in cell-surface IGF-IR concentrations and IGF-I action. Loss-of-function mutation of tumor suppressors, a common theme in human cancer, can lead to aberrant regulation of IGF-IR gene expression.