title: Signal transduction pathway of the induction of cell motility in hamster pancreatic ductal adenocarcinoma cell.
abstract: Recently, we reported that low (PC-1)- and high-invasive cell lines (PC-1.0) were established on the basis of hamster pancreatic ductal adenocarcinomas, and PC-1.0 cells were secreting the dissociation factor in the supernatant (DF-CM) which induced cell dissociation and enhancement 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 autocrine fashion by DF-CM. In contrast, cell motility of PC-1 was rapidly induced 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 using 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 was closely associated with their induction of cell motility. To elucidate these differences of responses against DF-CM between PC-1 and PC-1.0, signal transduction pathways of induction of the cell motilities were analyzed, using protein kinase C (PKC) inhibitor, 12-O-tetradecanoylphorbol-13-acetate, cyclic AMP antagonist, and cyclic AMP agonist. The transiently enhanced cell motility of DF-CM-treated PC-1 cells was completely inhibited by the cyclic AMP antagonist, and the cyclic AMP agonist was able to induce a similar pattern of induction of cell motility in PC-1 cells to DF-CM. On the other hand, the highly enhanced cell motility of PC-1.0 was completely inhibited by protein kinase C inhibitor, but not by cyclic AMP antagonist. These results suggest that cell motility of low-invasive PC-1 cells is under control through cyclic AMP-dependent protein kinase A, while the protein kinase C pathway seems favorable for high-invasive PC-1.0 cells to maintain the continuously enhanced cell motility responsible for their high invasiveness.
authors.affiliation: Department of Surgery II, Kumamoto University Medical School, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Akagi
authors.forename: H
authors.initials: H
authors.lastname: Egami
authors.forename: T
authors.initials: T
authors.lastname: Kurizaki
authors.forename: H
authors.initials: H
authors.lastname: Ohmachi
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D006224:Cricetinae; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D009361:Neoplasm Invasiveness; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D017077:Culture Media, Conditioned; D016376:Oligonucleotides, Antisense