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Updated: Aug 30, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Role of the androgen receptor axis in prostate cancer
1Department of Urology, University of Innsbruck, Innsbruck, Austria. zoran.culig@uibk.ac.at
Abstract:
Androgen receptor (AR) is expressed in nearly all prostate cancers, including treatment-refractory disease. The role of this receptor in the molecular endocrinology of prostate cancer has become increasingly clear in recent years. The AR is now known to participate in tumor progression through 3 mechanisms: expression (activation and upregulation of receptor activity), point mutations, and ligand-independent activation. With regard to the latter mechanism, interleukin-6 (IL-6) is among the most important nonsteroidal regulators of AR activity. In the absence of androgen, IL-6 causes activation of AR that is approximately 50% of the maximal activity induced by androgen. At low concentrations of androgen, IL-6 and androgen synergistically activate AR. Nonsteroidal antiandrogens usually antagonize this activation, but they switch to an agonist effect in the presence of oncostatin M, an IL-6-related cytokine. The growth of parental LNCaP cells is initially inhibited by exposure to IL-6, but long-term treatment renders the cells resistant to such inhibition and confers a growth advantage. Both IL-6 and oncostatin M stimulate AR activity, but only oncostatin M is associated with strong acquisition of the agonist properties of nonsteroidal antiandrogens. It is hoped that continuing research on AR expression and function in prostate cancer will pave the way for new therapeutic strategies.
Insights
Interleukin-6 (IL-6) activates the androgen receptor (AR) in prostate cancer cells, promoting tumor growth. This nonsteroidal regulator plays a key role in treatment-refractory disease progression.
Area of Science:
- Oncology
- Molecular Endocrinology
- Cancer Biology
Background:
- Androgen receptor (AR) is crucial in prostate cancer, even in treatment-resistant forms.
- AR signaling drives tumor progression via expression, mutations, and ligand-independent activation.
- Interleukin-6 (IL-6) is a key nonsteroidal regulator of AR activity.
Purpose of the Study:
- To investigate the role of IL-6 and related cytokines in AR activation and prostate cancer progression.
- To understand the mechanisms of ligand-independent AR activation in prostate cancer.
- To explore the synergistic effects of IL-6 and androgens on AR activity.
Main Methods:
- Investigated AR activation by IL-6 in the absence and presence of androgens.
- Examined the effects of IL-6 and oncostatin M on AR activity in LNCaP cells.
- Assessed the impact of nonsteroidal antiandrogens in combination with oncostatin M.
Main Results:
- IL-6 activates AR independently of androgens, with synergistic effects at low androgen concentrations.
- Long-term IL-6 exposure leads to resistance to growth inhibition and confers a growth advantage in LNCaP cells.
- Oncostatin M, but not IL-6 alone, promotes agonist effects of nonsteroidal antiandrogens.
Conclusions:
- IL-6 is a significant nonsteroidal regulator of AR activity in prostate cancer.
- IL-6 and oncostatin M influence AR signaling and prostate cancer cell behavior.
- Further research into AR function may lead to novel therapeutic strategies for prostate cancer.
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