RESUMEN
Retinoids exert wide-spectrum anti-tumor activities, which are mediated via the induction of growth arrest, differentiation or apoptosis. To determine whether the effects of retinoids are mediated by specific gene activation or repression, SC-M1 CL23 gastric cancer cells, pretreated with either vehicle alone or all-trans retinoic acid (10 microM) for 1 day, were analyzed using the technique of differential display. A novel retinoid-inducible gene 1 (RIG1) was isolated. The full-length RIG1 cDNA contained 768 base pairs and encoded a protein of 164 amino acids with a molecular weight of 18 kDa. The RIG1 gene was ubiquitously expressed in normal tissue, and its expression was positively associated with cellular density. Nucleotide sequence analysis demonstrated that the RIG1 gene was similar to a recently-isolated TIG3 gene, and displayed 54% nucleotide sequence homology with a type II tumor suppressor gene H-REV-107-1. RIG1 cDNA, however, contained an extra 32 base pairs located at its 5' end and revealed three base pair differences for the remaining sequences leading to two amino acids substitution between the two encoded proteins. All-trans retinoic acid increased the level of RIG1 mRNA in a time- and concentration-dependent manner in SC-M1 CL23 gastric cancer cells. This was not observed for the H-REV-107-1 gene. The RIG1 regulation was related to cellular retinoid sensitivity. Both retinoic acid receptor alpha- and retinoic acid receptor gamma-selective agonists increased RIG1 mRNA level, and the retinoid x receptor-selective agonist potentiated this regulation. In conclusion, the cDNA of a novel retinoid-inducible gene RIG1 has been cloned. This gene is regulated by retinoic acid through the heterodimer of retinoic acid receptor and retinoid x receptor.
Asunto(s)
Proteínas Portadoras/genética , Genes Supresores de Tumor , Receptores de Ácido Retinoico , Neoplasias Gástricas/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Secuencia de Bases , Clonación Molecular , Cartilla de ADN/genética , ADN Complementario/genética , ADN de Neoplasias/genética , Expresión Génica/efectos de los fármacos , Genes Supresores de Tumor/efectos de los fármacos , Humanos , Péptidos y Proteínas de Señalización Intracelular , Datos de Secuencia Molecular , Fosfolipasas A2 Calcio-Independiente , Proteínas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Retinoides/farmacología , Homología de Secuencia de Aminoácido , Transducción de Señal , Neoplasias Gástricas/metabolismo , Distribución Tisular , Células Tumorales Cultivadas , Proteínas Supresoras de TumorRESUMEN
Reinvestigation of the root of Rhinacanthus nasutus afforded, in addition to rhinacanthin-A to -D reported previously, two new dimethyldihydropyranonaphthoquinone esters (5, 6) and eight new 2-hydroxy-1,4-naphthoquinone esters (7-14) were isolated. The stereochemistry of rhinacanthin-A was determined as the R configuration. Compounds rhinacanthin-G to -N, belong to a class of 2-hydroxy-3-(3-hydroxy-2,2-dimethylpropyl)-1,4-naphthoquinone esters, and so far have been isolated only in this plant. Their biosynthesis is also discussed.