SIGNAL-TRANSDUCTION PATHWAY OF THE INDUCTION OF CELL MOTILITY IN HAMSTER PANCREATIC DUCTAL ADENOCARCINOMA CELL

Recently, we reported that low (PC-1)- and high-invasive cell lines (P C-1.0) were established on the basis of hamster pancreatic ductal aden ocarcinomas, and PC-1.0 cells were secreting the dissociation factor i n the supernatant (DF-CM) which induced cell dissociation and enhancem ent of cell motility. The cell motility of PC-1.0 is about 6 times as high as that of PC-1, which was continuously maintained in an autocrin e fashion by DF-CM. In contrast, cell motility of PC-1 was rapidly ind uced by DF-CM with a high level of induction of endogenous c-fos mRNA and returned to a basal level within 6 h. The inhibition experiment us ing antisense oligonucleotides to c-fos indicated that the high level of induction of c-fos mRNA observed in the DF-CM-treated PC-1 cells wa s closely associated with their induction of cell motility. To elucida te these differences of responses against DF-CM between PC-1 and PC-1. 0, signal transduction pathways of induction of the cell motilities we re analyzed, using protein kinase C (PKC) inhibitor, 12-O-tetradecanoy lphorbol-13-acetate, cyclic AMP antagonist, and cyclic AMP agonist. Th e transiently enhanced cell motility of DF-CM-treated PC-1 cells was c ompletely inhibited by the cyclic AMP antagonist, and the cyclic AMP a gonist was able to induce a similar pattern of induction of cell motil ity in PC-1 cells to DF-CM. On the other hand, the highly enhanced cel l motility of PC-1.0 was completely inhibited by protein kinase C inhi bitor, but not by cyclic AMP antagonist. These results suggest that ce ll motility of low-invasive PC-1 cells is under control through cyclic AMP-dependent protein kinase A, while the protein kinase C pathway se ems favorable for high-invasive PC-1.0 cells to maintain the continuou sly enhanced cell motility responsible for their high invasiveness.