Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma

Previous investigations have shown that interleukin-6, a member of the JAK- STAT activating family of cytokines, plays an important role in prostate ca rcinoma. Here we demonstrate the co-expression of another member of this cy tokine family, interleukin-11 (IL-11), and components of its receptor (inte rleukin-11 receptor; IL-11R), ie, IL-11R alpha (involved in ligand recognit ion), and gp130 (involved in signal transduction) in cultured normal and ma lignant prostate-derived epithelial cell lines. In the DU-145 prostate carc inoma cell line, rhIL-11 stimulates a transient and dose-dependent increase in the tyrosine 705-phosphorylated, active form of STAT3 (STAT3 P-Tyr705), involved in the downstream signaling of IL-11R and other members of the gp 130-dependent receptors. The ability of IL-11 to activate STAT3 in prostate -derived cells may be mechanistically important, given recent data suggesti ng that constitutively activated STAT3 may be associated with the malignant phenotype. In 51 human primary tissues derived from normal prostate, benig n prostatic hyperplasia, and prostate carcinomas, IL-11R alpha and gp130 we re commonly expressed, with a statistically significant elevation in the ex pression of IL-11R alpha in prostate carcinoma. Also, the tyrosine-phosphor ylated, activated form of STAT3 was observed more prominently in the nuclei of cells residing in malignant glands compared to those in nonmalignant sa mples. Thus, the IL-11 receptor system is up-regulated in prostate carcinom a, and may be one part of a cytokine network that maintains STAT3 in its ac tivated form in these tissues.