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

Jennifer D. Wu, Kathy Haugk, Libby Woodke, Peter Nelson, Ilsa Coleman, Stephen R. Plymate*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

137 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)392-401
Number of pages10
JournalJournal of Cellular Biochemistry
Volume99
Issue number2
DOIs
StatePublished - Oct 1 2006

Keywords

  • AR co-regulators
  • Androgen receptor (AR)
  • Androgen-independent (AI) prostate cancer
  • Insulin-like growth factor type I receptor (IGF-IR)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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