Transcriptional and epigenetic control of IGF1R gene expression: Implications in metabolism and cancer

Haim Werner*, Rive Sarfstein

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations

Abstract

IGF1R plays an important role in protection from apoptosis, regulation of cell growth, differentiation and oncogenic transformation. IGF1R aberrations lead to intrauterine and postnatal growth failure, microcephaly, mental retardation and deafness. High levels of IGF1R are detected in a diversity of human tumors. IGF1R gene transcription is controlled by complex interactions involving DNA-binding and non DNA-binding transcription factors. This review highlights selected examples of a series of tumor suppressors, including the breast cancer gene-1 (BRCA1), p53, the Wilm's tumor protein-1 (WT1) and the von Hippel-Lindau gene (VHL), whose mechanisms of action involve regulation of IGF1R gene expression. IGF1R gene transcription is also dependent on the presence of stimulatory nuclear proteins, including zinc-finger protein Sp1, EWS-WT1, E2F1, Krüppel-like factor-6 (KLF6), high-mobility group A1 (HMGA1), and others. Loss-of-function of tumor suppressor genes, usually caused by mutations, may result in non-functional proteins unable to control IGF1R promoter activity. Impaired regulation of the IGF1R gene is linked to defective cell division, chromosomal instability and increased incidence of cancer.

Original languageEnglish
Pages (from-to)112-118
Number of pages7
JournalGrowth Hormone and IGF Research
Volume24
Issue number4
DOIs
StatePublished - Aug 2014

Funding

FundersFunder number
European Foundation
Insulin-Dependent Diabetes Trust
US - Israel Binational Science Foundation
Israel Cancer Research Fund
Tel Aviv University

    Keywords

    • Cancer
    • IGF1R
    • IGF1R promoter
    • Transcription factors
    • Tumor suppressors

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