Skip Navigation


Carcinogenesis Advance Access originally published online on May 16, 2008
Carcinogenesis 2008 29(6):1148-1156; doi:10.1093/carcin/bgn109
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
29/6/1148    most recent
bgn109v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Seaton, A.
Right arrow Articles by Waugh, D. J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Seaton, A.
Right arrow Articles by Waugh, D. J. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Angela Seaton, Paula Scullin, Pamela J. Maxwell, Catherine Wilson, Johanna Pettigrew, Rebecca Gallagher, Joe M. O'Sullivan, Patrick G. Johnston and David J. J. Waugh*

Centre for Cancer Research and Cell Biology, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK

* To whom correspondence should be addressed. Tel: +44 2890 972760; Fax: +44 2890 972776; Email: d.waugh{at}qub.ac.uk

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.

Abbreviations: AIPC, androgen-independent prostate cancer; AR, androgen receptor; CaP, prostate cancer; Cdk2, cyclin-dependent kinase 2; CXCR, CXC chemokine receptor; DMSO, dimethyl sulphoxide; HEPES, N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid; IL, interleukin; JNK, c-jun N-terminal kinase; mRNA, messenger RNA; PBS, phosphate-buffered saline; PCR, polymerase chain reaction; PSA, prostate-specific antigen; qPCR, quantitative real-time polymerase chain reaction; rh-IL-8, recombinant human interleukin-8; TBS-T, Tris-buffered saline/0.1% Tween-20

Received December 20, 2007; revised April 11, 2008; accepted April 28, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Endocr Relat CancerHome page
D. Vindrieux, P. Escobar, and G. Lazennec
Emerging roles of chemokines in prostate cancer
Endocr. Relat. Cancer, September 1, 2009; 16(3): 663 - 673.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
H. Neuwirt, M. Puhr, F. R. Santer, M. Susani, W. Doppler, G. Marcias, V. Rauch, M. Brugger, A. Hobisch, L. Kenner, et al.
Suppressor of Cytokine Signaling (SOCS)-1 Is Expressed in Human Prostate Cancer and Exerts Growth-Inhibitory Function through Down-Regulation of Cyclins and Cyclin-Dependent Kinases
Am. J. Pathol., May 1, 2009; 174(5): 1921 - 1930.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
K. Malinowska, H. Neuwirt, I. T Cavarretta, J. Bektic, H. Steiner, H. Dietrich, P. L Moser, D. Fuchs, A. Hobisch, and Z. Culig
Interleukin-6 stimulation of growth of prostate cancer in vitro and in vivo through activation of the androgen receptor
Endocr. Relat. Cancer, March 1, 2009; 16(1): 155 - 169.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. J.J. Waugh and C. Wilson
The Interleukin-8 Pathway in Cancer
Clin. Cancer Res., November 1, 2008; 14(21): 6735 - 6741.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
C. Wilson, T. Wilson, P. G. Johnston, D. B. Longley, and D. J.J. Waugh
Interleukin-8 signaling attenuates TRAIL- and chemotherapy-induced apoptosis through transcriptional regulation of c-FLIP in prostate cancer cells
Mol. Cancer Ther., September 1, 2008; 7(9): 2649 - 2661.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.