Modulation of pancreatic tumor potential by overexpression of protein kinase C β1.

Overview

OBJECTIVE: This study aimed to investigate whether the overexpression of protein kinase C β1 (PKCβ1) is able to modulate the malignant phenotype displayed by the human ductal pancreatic carcinoma cell line PANC1. METHODS: PKCβ1 overexpression was achieved using a stable transfection approach. PANC1-PKCβ1 and control cells were analyzed both in vitro and in vivo. RESULTS: PANC1-PKCβ1 cells displayed a lower growth capacity associated with the down-regulation of the MEK/ERK pathway and cyclin expression. Furthermore, PKCβ1 overexpression was associated with an enhancement of cell adhesion to fibronectin and with reduced migratory and invasive phenotypes. In agreement with these results, PANC1-PKCβ1 cells showed an impaired ability to secrete proteolytic enzymes. We also found that PKCβ1 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-κB pathways. Most notably, the overexpression of PKCβ1 completely abolished the ability of PANC1 cells to induce tumors in nude mice. CONCLUSIONS: Our results established an important role for PKCβ1 in PANC1 cells suggesting it would act as a suppressor of tumorigenic behavior in pancreatic cancer.