Elevated levels of IGF-1 receptor convey invasive and metastatic capability in a mouse model of pancreatic islet tumorigenesis

Cancer Cell. 2002 May;1(4):339-53. doi: 10.1016/s1535-6108(02)00055-7.


In a prototypical model of multistage tumorigenesis involving pancreatic islets in RIP1-Tag2 transgenic mice, activation of insulin-like growth factor II (IGF-II) was previously shown to serve as a survival factor that inhibited apoptosis. Now IGF-1R, the receptor tyrosine kinase for IGF-II, has been found to be variably upregulated, first uniformly in dysplastic and angiogenic progenitors and then focally at the margins and in invasive regions of carcinomas. When the levels of IGF-1R were forcibly elevated throughout islet tumorigenesis, progression was accelerated at all stages in the pathway, although apoptosis was not differentially suppressed. Notably, encapsulated tumors were absent; instead, invasive carcinomas with downregulated E-cadherin were prevalent, and the majority of mice had local lymph node metastasis.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Bromodeoxyuridine
  • Cadherins / metabolism
  • Carcinoma, Islet Cell / metabolism*
  • Carcinoma, Islet Cell / secondary
  • Cell Division
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Flow Cytometry
  • Humans
  • In Situ Nick-End Labeling
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism*
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Up-Regulation
  • beta-Glucosidase / genetics
  • beta-Glucosidase / metabolism


  • Cadherins
  • DNA-Binding Proteins
  • IGHMBP2 protein, human
  • Ighmbp2 protein, mouse
  • Transcription Factors
  • Receptor, IGF Type 1
  • beta-Glucosidase
  • Bromodeoxyuridine