IGF1 receptor expression protects against microenvironmental stress found in the solid tumor.
The insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase, transmembrane receptor expressed in most body tissues and required for normal growth of cells. In cell culture, overexpression of the receptor has been shown to promote transformation and enhance cell survival in response to selected cytotoxic agents. As tumors develop, abnormalities in vascularization lead to a heterogeneous environment that includes areas of hypoxia, low pH and low glucose. Here we report that the overexpression of the IGF1R promotes increased survival in cells exposed to hypoxia, low pH and low glucose. Furthermore, cells lacking the receptor due to targeted disruption of the IGF1R gene do not survive as well as normal cells in such conditions. In addition, we find that cells can activate the IGF1R gene promoter in response to these conditions, and immunoblot analyses show increased receptor protein levels in cell exposed to hypoxia. Our results suggest a pathway of cancer cell adaptation to the tumor microenvironment in which conditions of the environment may induce expression of IGF1R, and this subsequent overexpression of the receptor may increase cell survival in such conditions.
Peretz
Shani
S
Departments of Therapeutic Radiology, Yale University School of Medicine, P.O. Box 208040, New Haven, Connecticut 06520-8040, USA.
Kim
Charlotte
C
Rockwell
Sara
S
Baserga
Renato
R
Glazer
Peter M
PM
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D015687:Cell Hypoxia / Q000502:physiology; D002470:Cell Survival; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
D011993:Recombinant Fusion Proteins; D008156:Luciferases; D017526:Receptor, IGF Type 1; D005947:Glucose