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

• Published in: British journal of cancer Vol. 97; no. 3; pp. 378 - 383
• Main Authors: TAM, L, MCGLYNN, L. M, TRAYNOR, P, MUKHERJEE, R, BARTLETT, J. M. S, EDWARDS, J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 06.08.2007
• Subjects: Ablation; Aged; Androgens; Apoptosis; Biological and medical sciences; Cancer research; Cell growth; Humans; Immunohistochemistry; Janus Kinases - metabolism; Ligands; Male; Medical research; Medical sciences; Middle Aged; Molecular Diagnostics; Neoplasms, Hormone-Dependent - metabolism; Nephrology. Urinary tract diseases; Patients; Prostate cancer; Prostatic Neoplasms - metabolism; Research ethics; Retrospective Studies; STAT3 Transcription Factor - metabolism; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; United Kingdom > UK; IL-6R; Treatment resistance; Urinary system disease; Prostate disease; Hormone therapy; Cytokine; Malignant tumor; IL-6; hormone refractory; Interleukin 6; Signal transduction; Interleukin-6 receptor; STAT; Cancerology; JAK; prostate; Transduction factor STAT; Male genital diseases; Prostate cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6603871

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(Tyr705) and pSTAT3(Ser727) 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 (P=0.0074) while an increase in expression of cytoplasmic pSTAT3(Tyr705) was associated with reduced patient survival (P=0.0003). In addition, those patients with high expression of cytoplasmic pSTAT3(Tyr705) 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(Tyr705) (P=0.002 and P=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.