Dysregulation of the Type 1 IGF receptor as a paradigm in tumor progression

Research output: Contribution to journalReview articlepeer-review

Abstract

The Type 1 IGF receptor plays a critical role in cell progression. During normal ontogeny it is expressed by every proliferating cell, where it functions as a potent cell survival agent. Disruption of the Type 1 IGF receptor gene by homologous recombination results in severely growth retarded animals which invariably die at birth. Most importantly, fibroblasts derived from mice embryos lacking the receptor cannot be transformed by any of a number of oncogenes, indicating that the Type 1 IGF receptor displays potent mitogenic and antiapoptotic activities. A number of transcription factors have been identified that control the expression of the IGF receptor promoter, thus stimulating cellular proliferation. On the other hand, certain tumour suppressors including p53 and WT1 were shown to repress the activity of the IGF receptor promoter. Mutant forms of these and other tumour suppressors are potentially impaired in their ability to suppress expression of the IGF receptor gene, thus helping to expand neoplastic populations.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalMolecular and Cellular Endocrinology
Volume141
Issue number1-2
DOIs
StatePublished - 25 Jun 1998

Keywords

  • Cancer
  • Cell cycle
  • IGF-1 receptor
  • Transcription
  • Tumour suppressors

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