Lagarrigue S, Chaumontet C, Heberden C, Martel P, Gaillard-Sanchez I
Laboratoire de Nutrition et Sécurité Alimentaire, INRA, Jouy-en-Josas, France.
Cell Mol Biol Res. 1995;41(6):551-60.
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.
AP1是一种异二聚体复合物，由Jun和Fos癌基因家族的产物组成。原癌基因c-fos和c-jun作为众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。在本研究中，为了证明在已知为致癌作用负调节剂的食源分子的分子机制中可能存在对AP1转录活性的抑制作用，我们建立了两个过表达c-fos（43C系）或c-jun（RELcJ1系）癌蛋白的大鼠肝上皮（REL）细胞系。与自发转化的43C系不同，转染c-jun的REL细胞仅在暴露于12-O-十四烷酰佛波醇13-乙酸酯（TPA）后在体外发生转化。全反式维甲酸（RA）消除了43C系和TPA处理的RELcJ1细胞的转化，这表明尽管c-fos或c-jun过表达，RA仍可降低这些细胞中的AP1活性。此外，我们首次表明，作为蔬菜天然成分的类黄酮槲皮素仅抑制43C系的转化。转染c-fos的REL细胞的自发转化与结合TRE的c-fos/AP1复合物的出现有关，这表明c-fos/AP1复合物参与了槲皮素的抗转化机制。
