Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation.

Seaton, A.; Scullin, P.; Maxwell, P. J.; Wilson, C.; Pettigrew, J.; Gallagher, R.; O'Sullivan, J. M.; Johnston, P. G.; Waugh, D. J. J.

doi:10.1093/carcin/bgn109

Cited by 143Prostate Cancer Treatment and ResearchChemokine receptors and signalingSperm and Testicular Function

Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation.

Seaton, A., Scullin, P., Maxwell, P. J., Wilson, C., Pettigrew, J., Gallagher, R., O'Sullivan, J. M., Johnston, P. G. +1 more·2008·Carcinogenesis

DOI 10.1093/carcin/bgn109

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Abstract

The aim of our study was to assess the importance of the CXC chemokine and interleukin (IL)-8 in promoting the transition of prostate cancer (CaP) to the androgen-independent state. Stimulation of the androgen-dependent cell lines, LNCaP and 22Rv1, with exogenous recombinant human interleukin-8 (rh-IL-8) increased androgen receptor (AR) gene expression at the messenger RNA (mRNA) and protein level, assessed by quantitative polymerase chain reaction and immunoblotting, respectively. Using an androgen response element-luciferase construct, we demonstrated that rh-IL-8 treatment also resulted in increased AR transcriptional activity in both these cell lines, and a subsequent upregulation of prostate-specific antigen and cyclin-dependent kinase 2 mRNA transcript levels in LNCaP cells. Blockade of CXC chemokine receptor-2 signaling using a small molecule antagonist (AZ10397767) attenuated the IL-8-induced increases in AR expression and transcriptional activity. Furthermore, in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, coadministration of AZ10397767 reduced the viability of LNCaP and 22Rv1 cells exposed to bicalutamide. Our data show that IL-8 signaling increases AR expression and promotes ligand-independent activation of this receptor in two androgen-dependent cell lines, describing two mechanisms by which this chemokine may assist in promoting the transition of CaP to the androgen-independent state. In addition, our data show that IL-8-promoted regulation of the AR attenuates the effectiveness of the AR antagonist bicalutamide in reducing CaP cell viability.

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Treatment of androgen-dependent LNCaP and CR 22Rv1 cells with recombinant IL-8 in the absence of serum results in cell growth in the absence and presence of androgen, concomitant with increased PSA mRNA expression.
“Treatment of androgen-dependent LNCaP and CR 22Rv1 cells with recombinant IL-8 in the absence of serum resulted in cell growth in the absence and presence of androgen, concomitant with increased PSA mRNA expression (30).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [30]

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Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation. Carcinogenesis 29: 1148-1156. doi:10.1093/carcin/bgn109. PubMed
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Authors: Seaton, A., Scullin, P., Maxwell, P. J., Wilson, C., Pettigrew, J., Gallagher, R., O'Sullivan, J. M., Johnston, P. G., & Waugh, D. J. J.
Affiliations: Queen's University Belfast (GB)
Corresponding author: Waugh, D. J. J.
ORCID: Maxwell, P. J.
Wilson, C.
Waugh, D. J. J.
Venue: Carcinogenesis
Publisher: Oxford University Press (OUP)
Published: 2008-04-15
Volume: 29
Issue: 6
Pages: 1148-1156
ISSN: 0143-3334 (ISSN-L)
1460-2180
DOI: 10.1093/carcin/bgn109
OpenAlex: W2123910382
Cited by: 143
References: 47
Citations by year: 2026: 1 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 3 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 6 · 2017: 11 · 2016: 5 · 2015: 12 · 2014: 6 · 2013: 20 · 2012: 14
FWCI: 8.87
Type: journal article
Language: en
Open access: closed
Locations: Carcinogenesis (publishedVersion)
PubMed (publishedVersion)
Research Portal (Queen's University Belfast) (submittedVersion)
Funders: AstraZeneca
Baylor University
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords: interleukin-8, prostate cancer, androgen receptor, bicalutamide resistance, ligand-independent receptor activation, prostate-specific antigen, CDK2, LNCaP cells, 22Rv1 cells
MeSH terms: Androgen Antagonists, Anilides, Flow Cytometry, Humans, Male, Nitriles, Prostatic Neoplasms, Receptors, Androgen, Tosyl Compounds, Transfection, Blotting, Western, Signal Transduction, Interleukin-8, Antineoplastic Agents, Hormonal, Drug Resistance, Neoplasm, Reverse Transcriptase Polymerase Chain Reaction, Receptors, Interleukin-8B, RNA, Small Interfering, Cell Line, Tumor, Cell Proliferation

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Interleukin-8 signaling promotes androgen-independent proliferation of prostate cancer cells via induction of androgen receptor expression and activation.

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