Identification of an enhancer involved in the melanoma-specific expression of the tumor antigen melanotransferrin gene.
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.
Duchange
N
N
Laboratoire d'Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France.
Ochoa
A
A
Plowman
G D
GD
Rozé
A
A
Amdjadi
M
M
Zakin
M M
MM
D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D004742:Enhancer Elements, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D058950:Melanoma-Specific Antigens; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D009838:Oligodeoxyribonucleotides; D016755:Proto-Oncogene Proteins c-jun