Functions of p38 mitogen-activated protein kinase alpha and beta in human pancreatic cancer cells

Abstract

The p38 family of mitogen-activated protein kinases (p38 MAPKs) includes p38α (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13). Among these four isoforms, p38α and p38β are widely expressed and are involved in regulating cell proliferation, cell differentiation and cell apoptosis. Nothing is presently known about the role of the p38 MAPKs in human pancreatic cancers. In this study, we characterized for the first time the effects of p38α and p38β on human pancreatic cancer cells. Expression of p38α and p38β were determined by immunoblot in 7 cultured human pancreatic cancer cell lines. ShRNA inhibition of endogenous p38α and p38β in Miapaca-2 and Panc-1 cells resulted in decreased anchorage-dependent and -independent growth. Single cell movement and cell invasion were markedly reduced in p38α shRNA expressing clones, but not altered in p38β shRNA expressing clones. And more dramatically, in contrast to in vitro invasion, in vivo tumorigenicity was decreased in p38β shRNA expressing clones rather than p38α shRNA expressing clones. We conclude that p38α and p38β may function synergistically in the tumor genesis of pancreatic cancer. Selective targeting may result in individualized treatment depending on the activity pattern in the future.