Proteinase-activated receptor-2-mediated signaling and inhibition of DNA synthesis in human pancreatic cancer cells.
CONCLUSIONS
Proteinase-activated receptor-2 (PAR-2)-mediated effects contribute to the intracellular signaling network in pancreatic tumor cells. A role of PAR-2 as negative regulator in human pancreatic tumor growth might be implied.


BACKGROUND
Using the human pancreatic tumor cell line MIA PaCa-2, we evaluated cellular effects of trypsin and the PAR-2-activating peptide SLIGRL on [Ca2+]i mobilization, Ins(1,4,5)P3 level, and protein kinase (PKC) activation. Furthermore, PAR-2 involvement in the regulation of cell proliferation has been estimated by measurement of [3H]thymidine incorporation in MIA PaCa-2 cells.


RESULTS
Trypsin and the PAR-2 synthetic peptide agonist SLIGRL induced [Ca2+]i mobilization, transient increase in inositol (1,4,5) triphosphate level, and PKC translocation in MIA PaCa-2 cells. In addition, SLIGRL induced a decrease in DNA synthesis in MIA PaCa-2 cells.
Kaufmann
R
R
Research Group Pharmacological Hemostaseology, Medical Faculty, Friedrich Schiller-University Jena, Germany. rol@bug.mpg.uni-jena.de
Schafberg
H
H
Nowak
G
G
D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004247:DNA / Q000037:antagonists & inhibitors*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D015544:Inositol 1,4,5-Trisphosphate; D004247:DNA; D011493:Protein Kinase C; D002118:Calcium; D013936:Thymidine