Cited by 188Prostate Cancer Treatment and ResearchGrowth Hormone and Insulin-like Growth FactorsSperm and Testicular Function

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

Wu, Jennifer D., Haugk, Kathy, Woodke, Libby, Nelson, Peter, Coleman, Ilsa, Plymate, Stephen R.·2006·Journal of Cellular Biochemistry

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.

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Crossref · 10.1002/jcb.20929

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  • In addition to being a target of AR transcriptional activity in prostate epithelial cells, the IGF-I receptor can induce intracellular signaling cascades that regulate phosphorylation of the AR, thus affecting its transcriptional activation both in the presence and absence of androgen.

    “In addition to being a target of AR transcriptional activity in prostate epithelial cells, IGF-I receptor can induce intracellular signaling cascades that regulate phosphorylation of the AR, thus affecting its transcriptional activation both in the presence and absence of androgen (37).”
  • The expression of both IGF-I and its receptor are increased in advanced cancers, especially in metastases.

    “The expression of both IGF-I and its receptor are increased in advanced cancers, especially in metastases (37).”

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Authors
Wu, J. D., Haugk, K., Woodke, L., Nelson, P., Coleman, I., & Plymate, S. R.
Affiliations
  • University of Washington (US)
  • VA Puget Sound Health Care System (US)
  • Fred Hutch Cancer Center (US)
Corresponding author
Plymate, Stephen R.
Venue
Journal of Cellular Biochemistry
Publisher
Wiley
Published
2006-04-25
Volume
99
Issue
2
Pages
392-401
ISSN
  • 0730-2312 (ISSN-L)
  • 1097-4644
OpenAlex
W1999859219
Cited by
188
References
49
Citations by year
2026: 1 · 2025: 1 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 9 · 2020: 12 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 7 · 2015: 9 · 2014: 17 · 2013: 14 · 2012: 14
FWCI
2.69
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Cellular Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (P01CA085859, K01CA116002, P01CA85859)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
androgen receptor, prostate cancer progression, castration-resistant prostate cancer, receptor dephosphorylation, androgen-regulated gene expression
MeSH terms
Animals, Cell Transformation, Neoplastic, Humans, Insulin-Like Growth Factor I, Male, Neoplasms, Hormone-Dependent, Prostatic Neoplasms, Receptors, Androgen, Somatomedins, Transplantation, Heterologous, Signal Transduction, Gene Expression, Receptor, IGF Type 1, Insulin-Like Growth Factor Binding Proteins, Active Transport, Cell Nucleus

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