title: Transcriptional and epigenetic control of IGF1R gene expression: implications in metabolism and cancer.
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.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: hwerner@post.tau.ac.il.
authors.forename: Haim
authors.initials: H
authors.lastname: Werner
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Rive
authors.initials: R
authors.lastname: Sarfstein
mesh_terms: D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017526:Receptor, IGF Type 1
keywords: Cancer; IGF1R; IGF1R promoter; Transcription factors; Tumor suppressors