Interaction of IGF signaling and the androgen receptor in prostate cancer progression.
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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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).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [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).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [37]
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Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer
Lamont, K. R., & Tindall, D. J. (2011) · Molecular Endocrinology · doi:10.1210/me.2010-0469 · Cited by 150 · see citing works
- 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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