TY - JOUR
T1 - Dysregulation of the Type 1 IGF receptor as a paradigm in tumor progression
AU - Werner, Haim
N1 - Funding Information:
The author wishes to thank Drs Illana Gozes, Charles T. Roberts, Jr., and Derek LeRoith for their helpful comments. The work in the author's laboratory is supported by grants from The John E. Fogarty International Center (National Institutes of Health, USA), The Ministry of Health of Israel, The Recanati Foundation, and The Israel Cancer Association. H.W. is the recipient of a Guastalla Fellowship, The Rashi Foundation, Israel.
PY - 1998/6/25
Y1 - 1998/6/25
N2 - 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.
AB - 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.
KW - Cancer
KW - Cell cycle
KW - IGF-1 receptor
KW - Transcription
KW - Tumour suppressors
UR - http://www.scopus.com/inward/record.url?scp=0032565914&partnerID=8YFLogxK
U2 - 10.1016/S0303-7207(98)00099-9
DO - 10.1016/S0303-7207(98)00099-9
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.systematicreview???
AN - SCOPUS:0032565914
SN - 0303-7207
VL - 141
SP - 1
EP - 5
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
IS - 1-2
ER -
