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

JD Wu, K Haugk, L Woodke, P Nelson… - Journal of cellular …, 2006 - Wiley Online Library
JD Wu, K Haugk, L Woodke, P Nelson, I Coleman, SR Plymate
Journal of cellular biochemistry, 2006Wiley Online Library
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 …
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. J. Cell. Biochem. 99: 392–401, 2006. © 2006 Wiley‐Liss, Inc.
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