p53 Regulates Insulin-Like Growth factor-I (IGF-I) Receptor Expression and IGF-I-induced Tyrosine Phosphorylation in an Osteosarcoma Cell Line: Interaction Between p53 and Sp1

Endocrinology. 1998 Mar;139(3):1101-7. doi: 10.1210/endo.139.3.5832.


The insulin-like growth factor-I receptor (IGF-IR) is involved in tumorigenesis. The aim of the present study was to investigate whether the IGF-IR is a physiological target for p53 in osteosarcoma cells. The p53-induced regulation of IGF-IR levels was studied in a tetracycline-regulated expression system. When expressed in Saos-2, osteosarcoma cells that lack p53, wild-type p53 decreased, whereas mutated p53 increased IGF-IR expression, and IGF-I-induced tyrosine phosphorylation of the IGF-IR. Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. A functional and physical interaction between p53 and Sp1, in the regulation of the IGF-R, was studied in osteosarcoma cells. Expression of p53 decreased IGF-IR promoter activity, whereas no effect on promoter activity was seen by Sp1 expressed alone. However, Sp1 counteracted the inhibitory effect of p53 on IGF-IR promoter activity in a dose-dependent manner. Furthermore, wild-type and mutated p53 were coimmunoprecipitated with Sp1, indicating a physical interaction between p53 and Sp1. In conclusion, p53 regulates IGF-IR expression, as reflected by a reduction in IGF-IR protein and a parallel reduction in IGF-I-induced tyrosine phosphorylation of the IGF-IR and IRS-1 in an osteosarcoma cell line. These data indicate that the IGF-I receptor is a physiological target for p53 in osteosarcoma cells. Furthermore, data supporting an interaction between p53 and Sp1 in the regulation of the promoter activity of IGF-IR are presented.

MeSH terms

  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Mutation
  • Osteosarcoma / metabolism*
  • Phosphorylation
  • Promoter Regions, Genetic
  • Receptor, IGF Type 1 / analysis*
  • Receptor, IGF Type 1 / genetics
  • Sp1 Transcription Factor / physiology*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology
  • Tyrosine / metabolism*


  • Sp1 Transcription Factor
  • Tumor Suppressor Protein p53
  • Tyrosine
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1