TY - JOUR
T1 - Transcriptional and epigenetic control of IGF1R gene expression
T2 - Implications in metabolism and cancer
AU - Werner, Haim
AU - Sarfstein, Rive
N1 - Funding Information:
Work in the laboratory of H.W. is supported by grants from the US - Israel Binational Science Foundation , Insulin-Dependent Diabetes Trust (IDDT, United Kingdom) , European Foundation for the Study of Diabetes , Tel Aviv University Cancer Biology Research Center , and Israel Cancer Research Fund (ICRF, Montreal, Canada). H.W. is the incumbent of the Lady Davis Chair in Biochemistry.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Cancer
KW - IGF1R
KW - IGF1R promoter
KW - Transcription factors
KW - Tumor suppressors
UR - http://www.scopus.com/inward/record.url?scp=84903710324&partnerID=8YFLogxK
U2 - 10.1016/j.ghir.2014.03.006
DO - 10.1016/j.ghir.2014.03.006
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AN - SCOPUS:84903710324
SN - 1096-6374
VL - 24
SP - 112
EP - 118
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
IS - 4
ER -