Opposing Oncogenic Functions of p38 Mitogen-activated Protein Kinase Alpha and Beta in Human Pancreatic Cancer Cells
Autor: | Marko Kornmann, S. Zhou, Uwe Knippschild, Benno Traub, Xiaodong Tian, Xuehai Xie, Doris Henne-Bruns |
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Rok vydání: | 2020 |
Předmět: |
Gene isoform
MAPK/ERK pathway Cancer Research Carcinogenesis p38 mitogen-activated protein kinases p38 Mitogen-Activated Protein Kinases Metastasis Mitogen-Activated Protein Kinase 14 Small hairpin RNA Mitogen-Activated Protein Kinase 11 Cell Line Tumor Pancreatic cancer medicine Humans Protein Isoforms Phosphorylation RNA Small Interfering Gene knockdown Kinase Chemistry General Medicine medicine.disease Gene Expression Regulation Neoplastic Pancreatic Neoplasms Oncology Cancer research |
Zdroj: | Anticancer Research. 40:5545-5556 |
ISSN: | 1791-7530 0250-7005 |
DOI: | 10.21873/anticanres.14567 |
Popis: | 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. |
Databáze: | OpenAIRE |
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