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

Background and aims: 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. However, little is known about the role of the p38 MAPKs in human cancers. The aim of this study was to elucidate possible functions of p38α and p38β in human pancreatic cancer.

Methods: Expression of p38α and p38β, p38γ and p38δ were determined by immunoblot in 7 cultured human pancreatic cancer cell lines. To selectively inhibit p38α or p38β, cell clones were established in a stable manner expression either p38α shRNA or p38β shRNA. Proliferation, single cell movement, migration and colony forming ability were determined in relation to p38 protein levels by cell counting, MTT assay, video-time laps microscopy, boyden-chamber and soft-agar assay, respectively.

Results: All pancreatic cancer cells showed p38 isoforms protein expression at various levels. Selective inhibition of p38α or p38β in MIA PaCa-2 and Panc-1 cells revealed that both kinases enhance cell proliferation and anchorage-independent growth. Single cell movement and cell invasion were markedly reduced in p38α shRNA expressing clones, but not altered in p38β shRNA expressing clones.

Conclusions: p38 MAPKs are expressed in pancreatic cancer cells and exert different functions. Selective targeting may result in individualized treatment depending on the activity pattern in the future.