title: Expression levels of the JAK/STAT pathway in the transition from hormone-sensitive to hormone-refractory prostate cancer.
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(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.
authors.affiliation: Section of Surgical and Translational Sciences, Division of Cancer Sciences and Molecular Pathology, Glasgow Royal Infirmary, Glasgow G31 2ER, UK.
authors.forename: L
authors.initials: L
authors.lastname: Tam
authors.forename: L M
authors.initials: LM
authors.lastname: McGlynn
authors.forename: P
authors.initials: P
authors.lastname: Traynor
authors.forename: R
authors.initials: R
authors.lastname: Mukherjee
authors.forename: J M S
authors.initials: JM
authors.lastname: Bartlett
authors.forename: J
authors.initials: J
authors.lastname: Edwards
mesh_terms: D000368:Aged; D006801:Humans; D007150:Immunohistochemistry; D053612:Janus Kinases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor; D053612:Janus Kinases