Adenovirus-mediated gene transfer of rasn17 inhibits specific cck
actions on pancreatic acinar cells.
Nicke, Barbara, Min-Jen Tseng, Marycarol Fenrich, and Craig D.
Logsdon.
Department of Physiology, University of Michigan, Ann Arbor, MI
48109-0622
APStracts 5:0311G, 1998.
Cholecystokinin (CCK) stimulates pleiotrophic responses in pancreatic
acinar cells, however, the intracellular signaling pathways involved
are not well understood. In order to evaluate the role of the ras
gene product in CCK actions, a strategy involving in vitro
adenoviral-mediated gene delivery of a dominant negative mutant ras
(rasN17) was utilized. Isolated acini were infected with various
titers of either a control adenovirus or an adenoviral construct
expressing rasN17 for 24 hours before being treated with CCK. Titer
dependent expression of rasN17 in the acini was confirmed by Western
blotting. Infection with control adenovirus (106 to 109 pfu/mg acinar
protein ([sim]1-1000 moi)) had no effect on CCK stimulation of acinar
cell amylase release, ERK or JNK kinases, or DNA synthesis. In
contrast, infection with adenovirus bearing rasN17 increased basal
amylase release, inhibited CCK mediated JNK activation, had no effect
on CCK activation of ERK, and inhibited DNA synthesis. These data
demonstrate important roles for ras in specific actions of CCK on
pancreatic acinar function.
Received 16 March 1998; accepted in final form 25 October 1998.
APS Manuscript Number G093-8.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 10 November 1998