Involvement of interleukin-6 and androgen receptor signaling in pancreatic cancer.

Pancreatic cancer remains one of the "difficult-to-treat" cancers. Signaling of androgen receptor (AR), one of the nuclear receptors, in the pancreas may be related to carcinogenesis. Higher interleukin-6 (IL-6) levels have been observed in pancreatic cancer patients. It is also well known that IL-6 affects the AR signaling pathway and that AR is important for cell migration activities. We demonstrated that IL-6 enhances the phosphorylation of STAT3 and MAPK, which in turn enhances AR-mediated transcription in pancreatic cancer cell lines. This activity was blocked by a pharmacological inhibitor of the JAK/STAT signaling pathway, AG490, and one of the MAPK signaling pathways, U0126. IL-6 also enhances pancreatic cancer cell migration in the presence of AR. This activity is blocked by AR-siRNA. IL-6 acts as a positive regulator in AR signaling, providing further insight into the progression of pancreatic carcinogenesis.