THE REGULATION OF IGF-I RECEPTOR GENE-EXPRESSION

The insulin-like growth factor I (IGF-I) receptor mediates most of the biological effects of IGF-I and -II. Despite its structural similarit y to the insulin receptor, the IGF-I receptor is mainly involved in th e transduction of growth and differentiation types of signals. The IGF -I receptor gene is constitutively expressed by most cells in the orga nism as well as in culture, consistent with the role of the IGFs as su rvival factors. In addition, the expression of the IGF-I receptor gene is modulated by a number of physiological and pathological factors, i ncluding developmental stage, nutritional status, hormones, growth dis orders and malignancy. The regulatory region of the IGF-I receptor gen e has been characterized and shown to display a high level of basal pr omoter activity. Transcription factor Sp1 is a strong activator of IGF -I receptor gene expression, whereas tumor suppressor WT1 represses it s activity. The biological implications of these findings in both norm al development and disease are described in this review.