sincalide and Carcinoma--Ductal--Breast

Growth of the human pancreatic carcinoma cell line KP-1N was stimulated with cholecystokinin (CCK)-8. A 40% increase in cell numbers was observed in the presence of 10(-10) MCCK-8 and this increase was inhibited by the addition of 25 microM CCK-A receptor antagonist (CR1505). The binding affinity of CCK-8 to KP-1N cells was 21-fold higher than that of gastrin 17-I. No significant increase in intracellular Ca2+ concentration was found upon stimulation with CCK-8. Components of signal transduction pathways that were activated in KP-1N cells after stimulation with CCK-8 were studied. CCK-8 stimulated tyrosine phosphorylation of a mitogen-activated protein kinase (MAPK) of approximately 42 kDa (p42map). c-Jun amino-terminal kinases (JNKs) of 46 kDa (p46jnk) and 55 kDa (p55jnk) were also activated by CCK-8 and increased the phosphorylation of c-Jun. CCK-8 at 10(-7) M induced 1.5-fold increases in the phosphorylation of MAPK and of c-Jun by JNKs, respectively. These results suggest that cell proliferation stimulated with CCK-8 in KP-1N cells may be mediated by signal transduction cascades leading to activation of JNKs and MAPKs.

Topics: Calcium-Calmodulin-Dependent Protein Kinases; Carcinoma, Ductal, Breast; Cell Division; Enzyme Activation; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Mitogen-Activated Protein Kinase Kinases; Pancreatic Neoplasms; Protein Kinases; Signal Transduction; Sincalide; Tumor Cells, Cultured