DIFFERENTIAL REGULATION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) RECEPTOR GENE-EXPRESSION BY IGF-I AND BASIC FIBROBLASTIC GROWTH-FACTOR

Insulin-like growth factor-I receptor (IGF-IR) gene expression is regu lated by various stimuli, including hormones, growth factors, and nutr itional status. We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fib roblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF inc reases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. This effect is mediated by a region of the IGF-IR promoter located be tween nucleotides -476 and -188 in the 5'-flanking region. In contrast , IGF-I decreases the IGF-IR mRNA levels. IGF-I down-regulates IGF-IR transcriptional activity as deduced from experiments in which the leve ls of pre-mRNA and mRNA were measured. IGF-I reduced pre-mRNA and mRNA levels in parallel, while the mRNA stability was found to be unchange d by IGF-I treatment. While these results strongly suggest an effect o f IGF-I on IGF-IR transcriptional activity, no specific IGF-I response element was demonstrated in the 5'-untranslated region or 5'-flanking region studied, Thus, bFGF and IGF-I have differential effects on IGF -IR gene transcription, with the IGF-I response region as yet unidenti fied.