Pancreatic cancer is the fourth leading cause of death in the US. Unlike other solid tumors such as testicular cancer which are now curable, more than 90% of pancreatic cancer patients die due to lack of response to therapy. Recently, the level of 14-3-3sigma mRNA was been found to be increased in pancreatic cancers and this increased expression may contribute to the failure in treatment of pancreatic cancers. In the present study, we tested this hypothesis.

Western blot analysis was used to determine 14-3-3sigma protein level in fresh frozen tissues and was correlated to clinical outcome. As stable cell line expressing 14-3-3sigma was established and the effect of 14-3-3sigmaover-expression on cellular response to radiation and anticancer drugs were tested using SRB assay. Cell cycle distribution and apoptosis analyses were performed using propidium iodide staining and PARP cleavage assays.

We found that 14-3-3sigma protein level was increased significantly in about 71% (17 of 24) of human pancreatic cancer tissues and that the 14-3-3sigma protein level in cancers correlated with lymph node metastasis and poor prognosis. Furthermore, we demonstrated that over-expression of 14-3-3sigma in a pancreatic cancer cell line caused resistance to gamma-irradiation as well as anticancer drugs by causing resistance to treatment-induced apoptosis and G2/M arrest.

The increased level of 14-3-3sigma protein likely contributes to the poor clinical outcome of human pancreatic cancers by causing resistance to radiation and anticancer drugs. Thus, 14-3-3sigma may serve as a prognosis marker predicting survival of pancreatic cancer patients and, thus, guide the clinical treatment of these patients.

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