Requirement of different signaling pathways mediated by insulin-like growth factor-I receptor for proliferation, invasion, and VPF/VEGF expression in a pancreatic carcinoma cell line

Biochem Biophys Res Commun. 2003 Feb 28;302(1):46-55. doi: 10.1016/s0006-291x(03)00107-4.

Abstract

Several oncogenes and growth factors are found to be mutated and overexpressed in adenocarcinoma of the pancreas, and may correlate with its highly aggressive nature. Insulin-like growth factor (IGF-I) and its receptor (IGF-IR) are highly expressed in this tumor type. We examined the IGF-IR-mediated signaling pathways in relation to cell proliferation, invasiveness, and expression pattern of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in the pancreatic cancer line ASPC-1. Our findings show that IGF-IR is an important growth factor receptor for cell proliferation and invasion, and VPF/VEGF expression in ASPC-1. Further experiments indicate that IGF-IR mediates different signaling pathways to execute its functions. Activation of Ras by IGF-IR was found to be required for the cell invasion. On the other hand Src activation through IGF-IR is required for the cell proliferation, invasion, and also VPF/VEGF expression. Taken together, our data indicate the importance of IGF-IR in growth and invasiveness of the pancreatic cancer cell lines and also point out the multiple signaling pathways channeled through this receptor.

Publication types

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

MeSH terms

  • Base Sequence
  • Cell Division / physiology*
  • DNA Primers
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Lymphokines / genetics
  • Lymphokines / metabolism*
  • Neoplasm Invasiveness*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Receptor, IGF Type 1 / physiology*
  • Signal Transduction / physiology*
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Up-Regulation
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • ras Proteins / metabolism

Substances

  • DNA Primers
  • Endothelial Growth Factors
  • Intercellular Signaling Peptides and Proteins
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins pp60(c-src)
  • ras Proteins