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 regulated by various stimuli, including hormones, growth factors, and nutritional status. We have investigated the molecular mechanism by which two growth factors, insulin-like growth factor-I (IGF-I) and basic fibroblast growth factor (bFGF) regulate IGF-IR gene expression. bFGF increases the endogenous IGF-IR mRNA levels and IGF-IR promoter activity. This effect is mediated by a region of the IGF-IR promoter located between 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 levels 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 unchanged by IGF-I treatment. While these results strongly suggest an effect of 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 unidentified.
Hernández-Sánchez
C
C
Section on Molecular and Cellular Physiology, Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1770, USA.
Werner
H
H
Roberts
C T
CT
Woo
E J
EJ
Hum
D W
DW
Rosenthal
S M
SM
LeRoith
D
D
D000818:Animals; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1