Neurotensin signaling induces intracellular alkalinization and interleukin-8 expression in human pancreatic cancer cells.

Abstract	Pancreatic adenocarcinomas express neurotensin receptors in up to 90% of cases, however, their role in tumor biology and as a drug target is not clear. In the present study, a stable neurotensin (NT) analog induced intracellular calcium release and intracellular alkalinization in BxPC-3 and PANC-1 pancreatic cancer cells that was abolished by inhibitors of NT receptor (NTR) and sodium-proton exchanger 1 (NHE1), amiloride and SR 142948, respectively. Activation of NHE1 involved increased phosphorylation of dimethylfumarate-sensitive mitogen- and stress-activated kinase 1/2 (MSK1/2). NTR signaling appears to promote a metastatic phenotype in pancreatic cancer cells by induction of localized extracellular acidification in normoxic cells, preceeding acidosis induced by hypoxia and switch to glycolysis in addition to increased expression of interleukin-8 (IL-8).
Authors	Ulrike Olszewski, Gerhard Hamilton
Journal	Molecular oncology (Mol Oncol) Vol. 3 Issue 3 Pg. 204-13 (Jun 2009) ISSN: 1878-0261 [Electronic] United States
PMID	19393580 (Publication Type: Journal Article)
Chemical References	CXCL8 protein, human Cation Transport Proteins Interleukin-8 Neoplasm Proteins Pyrazoles Quinolines Receptors, Neurotensin SLC9A1 protein, human SR 142948 Sodium Channel Blockers Sodium-Hydrogen Exchanger 1 Sodium-Hydrogen Exchangers Neurotensin Amiloride RPS6KA4 protein, human Ribosomal Protein S6 Kinases, 90-kDa mitogen and stress-activated protein kinase 1
Topics	Adenocarcinoma (metabolism, pathology) Amiloride (pharmacology) Cation Transport Proteins (metabolism) Cell Line, Tumor Gene Expression Regulation, Neoplastic Humans Interleukin-8 (biosynthesis) Neoplasm Metastasis Neoplasm Proteins (metabolism) Neurotensin (metabolism, pharmacology) Pancreatic Neoplasms (metabolism, pathology) Phosphorylation (drug effects) Pyrazoles (pharmacology) Quinolines (pharmacology) Receptors, Neurotensin (metabolism) Ribosomal Protein S6 Kinases, 90-kDa (metabolism) Signal Transduction Sodium Channel Blockers (pharmacology) Sodium-Hydrogen Exchanger 1 Sodium-Hydrogen Exchangers (metabolism)

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