Rapid induction of IGF-IR signaling in normal and tumor tissue following intravenous injection of IGF-I in mice.
The detection of IGF-IR signaling in animal models has important implications for determining the role of this receptor in normal physiology and tumor growth. While many reports have correlated changes in plasma IGF-I levels in vivo with biological responses, few have shown that altered IGF-I levels can directly affect signaling within normal or tumor tissue. Here, we present new data that shows how the intravenous (IV) injection of IGF-I can be used to directly examine IGF signaling at the tissue level. Tail-vein IV injection of IGF-I into mice resulted in a rapid and dose-dependent activation of the IGF-I receptor and downstream phosphorylation of Akt and ERK1/2 in liver, kidney, and mammary gland. Similarly, IV IGF-I rapidly stimulated signaling in HT-29 colorectal and in MCF-7 breast cancer xenografts. This study shows how IV IGF injection can be used to examine the signaling mechanisms used by IGF-IR, in both normal mammary tissue and during tumor growth, and may provide a model for the characterization of IGF inhibitors.
Lee
A V
AV
The Breast Center, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. avlee@breastcenter.tmc.edu
Taylor
S T
ST
Greenall
J
J
Mills
J D
JD
Tonge
D W
DW
Zhang
P
P
George
J
J
Fiorotto
M L
ML
Hadsell
D L
DL
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014183:Transplantation, Heterologous
D000906:Antibodies; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases