Rapid induction of IGF-IR signaling in normal and tumor tissue following intravenous injection of IGF-I in mice

Horm Metab Res. 2003 Nov-Dec;35(11-12):651-5. doi: 10.1055/s-2004-814141.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Injections, Intravenous
  • Insulin Receptor Substrate Proteins
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / pharmacology*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kinetics
  • Liver / drug effects
  • Liver / metabolism
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / metabolism
  • Mice
  • Mice, Nude
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphoproteins / immunology
  • Phosphorylation
  • Receptor, IGF Type 1 / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Transplantation, Heterologous

Substances

  • Antibodies
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, mouse
  • Phosphoproteins
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases