Modulation of Pancreatic Tumor Potential by Overexpression of Protein Kinase C β1

Objective: This study aimed to investigate whether the overexpression of protein kinase C beta 1 (PKC beta 1) is able to modulate the malignant phenotype displayed by the human ductal pancreatic carcinoma cell line PANC1. Methods: PKC beta 1 overexpression was achieved using a stable transfection approach. PANC1-PKC beta 1 and control cells were analyzed both in vitro and in vivo. Results: PANC1-PKC beta 1 cells displayed a lower growth capacity associated with the down-regulation of the MEK/ERK pathway and cyclin expression. Furthermore, PKC beta 1 overexpression was associated with an enhancement of cell adhesion to fibronectin and with reduced migratory and invasive phenotypes. In agreement with these results, PANC1-PKC beta 1 cells showed an impaired ability to secrete proteolytic enzymes. We also found that PKC beta 1 overexpressing cells were more resistant to cell death induced by serum deprivation, an event associated with G0/G1 arrest and the modulation of PI3K/Akt and NF-kappa B pathways. Most notably, the overexpression of PKC beta 1 completely abolished the ability of PANC1 cells to induce tumors in nude mice. Conclusions: Our results established an important role for PKC beta 1 in PANC1 cells suggesting it would act as a suppressor of tumorigenic behavior in pancreatic cancer.