Regulation of the insulin-like growth factor-I receptor gene by oncogenes and antioncogenes: implications in human cancer.
The insulin-like growth factor-I receptor (IGF-I-R) has a central role in normal cellular proliferation as well as in transformation processes. Transcription of the IGF-I receptor gene is controlled by a number of tumor suppressors, including WT1, p53, and BRCA1. It has been demonstrated that, in their wild-type form, these transcription factors can suppress the activity of the IGF-I-R promoter, with ensuing reduction in the levels of cell-surface IGF binding. On the other hand, a number of oncogenes, including mutant p53 and c-myb, and the fusion protein EWS-WT1 significantly stimulate promoter activity. Interactions between stimulatory and inhibitory transcription factors may determine the level of expression of the IGF-I-R gene and, consequently, the proliferative status of the cell.
Werner
H
H
Department of Clinical Biochemistry, Tel Aviv University, Tel Aviv, 69978, Israel. hwerner@post.tau.ac.il
Shalita-Chesner
M
M
Abramovitch
S
S
Idelman
G
G
Shaharabani-Gargir
L
L
Glaser
T
T
D017209:Apoptosis; D002453:Cell Cycle; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D009369:Neoplasms / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D009857:Oncogenes; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D013002:Somatomedins / Q000378:metabolism
D013002:Somatomedins; D017526:Receptor, IGF Type 1