S Lagarrigue, C Chaumontet, C Heberden, P Martel, I Gaillard-Sanchez
{"title":"槲皮素和维甲酸对大鼠肝上皮细胞癌基因诱导转化的抑制作用。","authors":"S Lagarrigue, C Chaumontet, C Heberden, P Martel, I Gaillard-Sanchez","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>AP1 is a heterodimeric complex containing products of the Jun and Fos oncogene families. The c-fos and c-jun protooncogenes act as transcriptional activator for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. In this study, to show evidence of a possible inhibition of AP1 transcriptional activity in molecular mechanisms of foodborne molecules, known to be negative modulators of carcinogenesis, we established two rat liver epithelial (REL) cell lines overexpressing either c-fos (43C line) or c-jun (RELcJ1 line) oncoproteins. Contrary to the 43C line, which was spontaneously transformed, the c-jun-transfected REL cells were only transformed in vitro after 12-O-tetra-decanoylphorbol 13-acetate (TPA) exposure. All trans-retinoic acid (RA) abolished the transformation of the 43C line and TPA-treated RELcJ1 cells, suggesting that RA could decrease AP1 activity in these cells despite c-fos or c-jun overexpression. Furthermore, we show for the first time that a flavonoid, quercetin, which is a natural component of vegetables, inhibited only the transformation of the 43C line. The spontaneous transformation of the c-fos-transfected REL cells was associated with the appearance of c-fos/AP1 complexes binding TRE, suggesting that c-fos/AP1 complexes are involved in the antitransforming mechanism of quercetin.</p>","PeriodicalId":72545,"journal":{"name":"Cellular & molecular biology research","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1995-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Suppression of oncogene-induced transformation by quercetin and retinoic acid in rat liver epithelial cells.\",\"authors\":\"S Lagarrigue, C Chaumontet, C Heberden, P Martel, I Gaillard-Sanchez\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>AP1 is a heterodimeric complex containing products of the Jun and Fos oncogene families. The c-fos and c-jun protooncogenes act as transcriptional activator for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. In this study, to show evidence of a possible inhibition of AP1 transcriptional activity in molecular mechanisms of foodborne molecules, known to be negative modulators of carcinogenesis, we established two rat liver epithelial (REL) cell lines overexpressing either c-fos (43C line) or c-jun (RELcJ1 line) oncoproteins. Contrary to the 43C line, which was spontaneously transformed, the c-jun-transfected REL cells were only transformed in vitro after 12-O-tetra-decanoylphorbol 13-acetate (TPA) exposure. All trans-retinoic acid (RA) abolished the transformation of the 43C line and TPA-treated RELcJ1 cells, suggesting that RA could decrease AP1 activity in these cells despite c-fos or c-jun overexpression. Furthermore, we show for the first time that a flavonoid, quercetin, which is a natural component of vegetables, inhibited only the transformation of the 43C line. The spontaneous transformation of the c-fos-transfected REL cells was associated with the appearance of c-fos/AP1 complexes binding TRE, suggesting that c-fos/AP1 complexes are involved in the antitransforming mechanism of quercetin.</p>\",\"PeriodicalId\":72545,\"journal\":{\"name\":\"Cellular & molecular biology research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1995-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular & molecular biology research\",\"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":"Cellular & molecular biology research","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
AP1是一种异二聚体复合体,含有Jun和Fos癌基因家族的产物。c-fos和c-jun原癌基因是许多细胞基因的转录激活因子,这些基因的过表达可能导致恶性转化。在这项研究中,为了证明AP1转录活性在食源性分子(已知是致癌的负调节因子)的分子机制中的可能抑制,我们建立了两个大鼠肝上皮(REL)细胞系,过表达c-fos (43C系)或c-jun (RELcJ1系)癌蛋白。与43C系自发转化不同,c-jun转染的REL细胞只有在暴露于TPA (12- o - tetrao -decanoylphorbol 13-acetate)后才能在体外转化。所有反式维甲酸(RA)都能消除43C细胞系和tpa处理的RELcJ1细胞的转化,这表明RA可以降低这些细胞中AP1的活性,尽管c-fos或c-jun过表达。此外,我们首次证明了一种类黄酮,槲皮素,是蔬菜的天然成分,只抑制43C系的转化。c-fos转染后REL细胞的自发转化与c-fos/AP1复合物结合TRE的出现有关,提示c-fos/AP1复合物参与槲皮素的抗转化机制。
Suppression of oncogene-induced transformation by quercetin and retinoic acid in rat liver epithelial cells.
AP1 is a heterodimeric complex containing products of the Jun and Fos oncogene families. The c-fos and c-jun protooncogenes act as transcriptional activator for numerous cellular genes, and the overexpression of these genes may cause malignant transformation. In this study, to show evidence of a possible inhibition of AP1 transcriptional activity in molecular mechanisms of foodborne molecules, known to be negative modulators of carcinogenesis, we established two rat liver epithelial (REL) cell lines overexpressing either c-fos (43C line) or c-jun (RELcJ1 line) oncoproteins. Contrary to the 43C line, which was spontaneously transformed, the c-jun-transfected REL cells were only transformed in vitro after 12-O-tetra-decanoylphorbol 13-acetate (TPA) exposure. All trans-retinoic acid (RA) abolished the transformation of the 43C line and TPA-treated RELcJ1 cells, suggesting that RA could decrease AP1 activity in these cells despite c-fos or c-jun overexpression. Furthermore, we show for the first time that a flavonoid, quercetin, which is a natural component of vegetables, inhibited only the transformation of the 43C line. The spontaneous transformation of the c-fos-transfected REL cells was associated with the appearance of c-fos/AP1 complexes binding TRE, suggesting that c-fos/AP1 complexes are involved in the antitransforming mechanism of quercetin.