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 similarity to the insulin receptor, the IGF-I receptor is mainly involved in the transduction of growth and differentiation types of signals. The IGF-I receptor gene is constitutively expressed by most cells in the organism as well as in culture, consistent with the role of the IGFs as survival factors. In addition, the expression of the IGF-I receptor gene is modulated by a number of physiological and pathological factors, including developmental stage, nutritional status, hormones, growth disorders and malignancy. The regulatory region of the IGF-I receptor gene has been characterized and shown to display a high level of basal promoter activity. Transcription factor Sp1 is a strong activator of IGF-I receptor gene expression, whereas tumor suppressor WT1 represses its activity. The biological implications of these findings in both normal development and disease are described in this review.