{"title":"仓鼠胰腺导管腺癌细胞诱导细胞运动的信号转导途径。","authors":"J Akagi, H Egami, T Kurizaki, H Ohmachi, M Ogawa","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14452,"journal":{"name":"Invasion & metastasis","volume":"17 1","pages":"16-25"},"PeriodicalIF":0.0000,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Signal transduction pathway of the induction of cell motility in hamster pancreatic ductal adenocarcinoma cell.\",\"authors\":\"J Akagi, H Egami, T Kurizaki, H Ohmachi, M Ogawa\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":14452,\"journal\":{\"name\":\"Invasion & metastasis\",\"volume\":\"17 1\",\"pages\":\"16-25\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1997-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Invasion & metastasis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Invasion & metastasis","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
最近,我们在仓鼠胰腺导管腺癌的基础上建立了低侵袭性(PC-1)和高侵袭性细胞系(PC-1.0), PC-1.0细胞在上清液中分泌解离因子(DF-CM),诱导细胞解离,增强细胞活力。PC-1.0的细胞活力约为PC-1的6倍,DF-CM使PC-1的细胞活力持续保持自分泌状态。相反,DF-CM高水平诱导PC-1细胞运动,并在6 h内恢复到基础水平。反意义寡核苷酸对c-fos的抑制实验表明,DF-CM处理PC-1细胞中c-fos mRNA的高水平诱导与其对细胞运动的诱导密切相关。为了阐明PC-1和PC-1.0对DF-CM的反应差异,我们使用蛋白激酶C (PKC)抑制剂、12- o -十四烷醇-13-乙酸酯、环AMP拮抗剂和环AMP激动剂,分析了诱导细胞运动的信号转导途径。经DF-CM处理的PC-1细胞短暂增强的细胞运动性被环AMP拮抗剂完全抑制,环AMP激动剂能够诱导PC-1细胞对DF-CM类似的细胞运动性诱导模式。另一方面,蛋白激酶C抑制剂能完全抑制PC-1.0细胞的运动,而环AMP拮抗剂则不能。这些结果表明,低侵袭性PC-1细胞的细胞运动性是通过环amp依赖的蛋白激酶A来控制的,而高侵袭性PC-1.0细胞的细胞运动性似乎是通过蛋白激酶C途径来维持的。
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 (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.