Opposing Oncogenic Functions of p38 Mitogen-activated Protein Kinase Alpha and Beta in Human Pancreatic Cancer Cells

Abstract

Background/aim: The p38 family of mitogen-activated protein kinases (MAPK) includes four isoforms: p38α, -β, -γ and -δ. The aim of this study was to elucidate possible functions of p38α and p38β in human pancreatic cancer.

Materials and methods: Isoform expression was determined in seven human pancreatic cancer cell lines. After shRNA based selective knockdown of p38α and p38β, in vitro growth and migration as well as in vivo tumorigenicity were assessed.

Results: All pancreatic cancer cells expressed p38 isoforms. Knockdown of p38α and p38β inhibited in vitro growth. Migration was markedly reduced in p38α shRNA expressing clones, but not altered by p38β knockdown. While in vivo inhibition of p38β decreased tumor formation and growth, the knockdown of p38α significantly enhanced tumorigenicity.

Conclusion: p38 MAPKs may exert isoform specific functions in pancreatic cancer. Selective targeting may contribute to individualized treatment of pancreatic cancer in the future.

Keywords: invasion; isoforms; metastasis; p38 mitogen-activated protein kinase; pancreatic cancer.