Interaction of IGF signaling and the androgen receptor in prostate cancer progression

J Cell Biochem. 2006 Oct 1;99(2):392-401. doi: 10.1002/jcb.20929.


The insulin-like growth factor type I receptor (IGF-IR) has been suggested to play an important role in prostate cancer progression and possibly in the progression to androgen-independent (AI) disease. The term AI may not be entirely correct, in that recent data suggest that expression of androgen receptor (AR) and androgen-regulated genes is the primary association with prostate cancer progression after hormone ablation. Therefore, signaling through other growth factors has been thought to play a role in AR-mediated prostate cancer progression to AI disease in the absence of androgen ligand. However, existing data on how IGF-IR signaling interacts with AR activation in prostate cancer are conflicting. In this Prospect article, we review some of the published data on the mechanisms of IGF-IR/AR interaction and present new evidence that IGF-IR signaling may modulate AR compartmentation and thus alter AR activity in prostate cancer cells. Inhibition of IGF-IR signaling can result in cytoplasmic AR retention and a significant change in androgen-regulated gene expression. Translocation of AR from the cytoplasm to the nucleus may be associated with IGF-induced dephosphorylation. Since fully humanized antibodies targeting the IGF-IR are now in clinical trials, the current review is intended to reveal the mechanisms of potential therapeutic effects of these antibodies on AI prostate cancers.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • Cell Transformation, Neoplastic
  • Gene Expression
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Neoplasms, Hormone-Dependent / etiology
  • Neoplasms, Hormone-Dependent / metabolism
  • Neoplasms, Hormone-Dependent / therapy
  • Prostatic Neoplasms / etiology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / therapy
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Receptors, Androgen / metabolism*
  • Signal Transduction
  • Somatomedins / metabolism*
  • Transplantation, Heterologous


  • Insulin-Like Growth Factor Binding Proteins
  • Receptors, Androgen
  • Somatomedins
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1