RESUMEN
The human iron-binding protein melanotransferrin is up-regulated in most skin melanomas. With the goal to understand the mechanisms controlling the expression of the gene in these tumor cells, we previously reported the identification of an enhancer exhibiting melanoma specificity. We show here that, in the highly expressing SK-MEL-28 melanoma cell line, the chromatin structure in the enhancer region is in an open configuration and that the transcription factors governing its activity belong to the helix-loop-helix and the Jun/Fos leucine zipper families.
Asunto(s)
Antígenos de Neoplasias/genética , Elementos de Facilitación Genéticos , Regulación Neoplásica de la Expresión Génica , Melanoma/genética , Proteínas de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Secuencia de Bases , Sitios de Unión , ADN de Neoplasias , Desoxirribonucleasa I/metabolismo , Células HeLa , Secuencias Hélice-Asa-Hélice , Humanos , Antígenos Específicos del Melanoma , Datos de Secuencia Molecular , Proteínas de Neoplasias/metabolismo , Factores de Transcripción/metabolismo , Activación Transcripcional , Células Tumorales CultivadasRESUMEN
Melanotransferrin (MTf) is a tumor associated antigen found in abundance on the surface of melanoma cells. It is a transferrin-like protein found in low amount in most adult tissues and whose gene is reminiscent of house-keeping genes. With the goal of understanding the regulatory mechanisms which might explain the enhancement of expression in tumor cells, we report here the characterization of a regulatory element located 2 kbp upstream from the promoter and whose deletion specifically impairs gene expression in melanoma cells; we show that this element is part of an enhancer composed of two modules which are each the target for the AP1 transcription factor. The two modules present a synergistic mode of action specific for melanoma cells which requires both of the 130 bp away AP1 sites. Furthermore, we show that the enhancer behaves differently according to the promoter context.