Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer

Tam, L., McGlynn, L.M., Traynor, P., Mukherjee, R., Bartlett, J.M.S. and Edwards, J. (2007) Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer. British Journal of Cancer, 97(3), pp. 378-383. (doi: 10.1038/sj.bjc.6603871)

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Publisher's URL: http://dx.doi.org/10.1038/sj.bjc.6603871

Abstract

The main cause of prostate cancer-related mortality is the development of hormone-refractory disease. Circulating serum levels of IL-6 are raised in hormone-refractory prostate cancer patients and evidence from cell line studies suggests that the IL-6R/JAK/STAT3 pathway may be involved in development of this disease. In the current study we investigate if expression levels of these family members are implicated in the development of hormone-refractory prostate cancer. Immunohistochemistry using IL-6R, JAK1, STAT3, pSTAT3<sup>Tyr705</sup> and pSTAT3<sup>Ser727</sup> antibodies was performed on 50 matched hormone-sensitive and hormone-refractory tumours pairs. An increase in expression of cytoplasmic IL-6 receptor, with the development of hormone-refractory prostate cancer was associated with reduced time to relapse (<i>P</i>=0.0074) while an increase in expression of cytoplasmic pSTAT3<sup>Tyr705</sup> was associated with reduced patient survival (<i>P</i>=0.0003). In addition, those patients with high expression of cytoplasmic pSTAT3<sup>Tyr705</sup> in their hormone-refractory tumours had significantly shorter time to death from biochemical relapse and overall survival in comparison to those patients with low expression of cytoplasmic pSTAT3<sup>Tyr705</sup> (<i>P</i>=0.002 and <i>P</i>=0.0027, respectively). Activation of STAT3, via phosphorylation is associated with reduced patient survival, suggesting that activation of the IL-6R/JAK/STAT3 pathway is involved with development of hormone-refractory prostate cancer.

Item Type:Articles
Keywords:Prostate, IL-6, IL-6R, JAK, STAT, hormone refractory
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McGlynn, Dr Liane and Edwards, Professor Joanne and McCall, Dr Pamela
Authors: Tam, L., McGlynn, L.M., Traynor, P., Mukherjee, R., Bartlett, J.M.S., and Edwards, J.
Subjects:R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:British Journal of Cancer
Publisher:Nature Publishing Group
ISSN:0007-0920
ISSN (Online):1532-1827
Published Online:26 June 2007
Copyright Holders:Copyright © 2007 Nature Publishing Group
First Published:First published in British Journal of Cancer 97(3):378-383
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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