Activating P2X7 Receptors Increases Proliferation of Human Pancreatic Cancer Cells via ERK1/2 and JNK. Issue 5 (May 2018)

• Record Type: Journal Article
• Authors: Choi, Ji Hun; Ji, Young Geon; Ko, Jung Jae; Cho, Han Jun; Lee, Dong Hyeon
• Is Part Of: Pancreas. Volume 47:Issue 5(2018)
• Publication Date: 2018-05
• Subjects: P2X7 -- proliferation -- pancreatic cancer cell -- extracellular signal-regulated protein kinases 1 and 2 -- c-Jun N-terminal kinase; Pancreas -- Diseases -- Periodicals; Pancreas -- Periodicals; Neuroendocrine tumors -- Periodicals; 616.37005
• DOI: 10.1097/MPA.0000000000001055
• Languages: English
• ISSNs: 0885-3177

Abstract

Abstract : Objectives: The aim of this study was to investigate the effects of the activated P2X7 receptors on the proliferation and growth of human pancreatic cancer cells. Methods: Proliferation was measured by incorporating bromodeoxyuridine into pancreatic cancer cells, MIA PaCa-2 and HPAC. Expression of P2 receptors and signal molecules was examined using quantitative reverse transcription/polymerase chain reaction and/or Western blot. Proliferative effects of the P2X7 receptors in vivo were examined using a xenotransplant model of pancreatic cancer cell lines. Results: Incubating pancreatic cancer cells with adenosine triphosphate (ATP) and 2′(3′)-O-(4-Benzoylbenzoyl)ATP resulted in a dose-dependent increase of cell proliferation. The P2 receptor antagonist, KN-62, and small interfering RNA against P2X7 receptors, significantly decreased the proliferative effects of ATP. The ATP-induced proliferation was mediated by protein kinase C, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and c-Jun N-terminal kinase (JNK); specifically, ATP increased the phosphorylation of ERK1/2 and JNK. The expression of inducible nitric oxide synthase was decreased by P2X7 receptor activation. In a xenotransplant model, applying ATP significantly increased the growth of induced tumors. Conclusions: The P2X7 receptor activation by extracellular nucleotides increased proliferation and growth of human pancreatic cancer cells via ERK1/2 and JNK. This supports the pathophysiological role of P2X7 receptors in pancreatic disease and recovery.