Melanotransferrin gene expression in melanoma cells is correlated with high levels of Jun/Fos family transcripts and with the presence of a specific AP1-dependent ternary complex.
The involvement of the transcription factor AP1 in the regulation of melanotransferrin (MTf) gene expression was investigated. MTf, also known as p97, is a tumour-associated antigen that is overproduced in most melanomas. Its gene expression is under the control of an enhancer element containing two AP1 binding sites. By Northern analysis, we demonstrate that MTf mRNA is detected at various levels in melanoma SK-MEL-28 cells and that its greatest expression coincides with the presence of large amounts of jun and fos transcripts. Gel retardation assays revealed that the induction of expression of these proto-oncogenes is correlated with increased AP1 binding activity and that a region of the MTf enhancer is involved in the formation of a ternary AP1-dependent complex, implicating a second nuclear factor whose binding characteristics are similar to those of nuclear factor of activated T cells (NF-AT). In transient expression experiments, the activity resulting from ternary complex formation was high and specific to melanoma cells. These data provide a possible explanation for the mechanisms of AP1 factor family involvement in MTf up-regulation in melanoma cells.
Rozé-Heusse
A
A
Unité d'Expression des Gènes Eucaryotes, Institut Pasteur, Paris, France.
Houbiguian
M L
ML
Debacker
C
C
Zakin
M M
MM
Duchange
N
N
D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D046911:Macromolecular Substances; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D058950:Melanoma-Specific Antigens; D050778:NFATC Transcription Factors; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D058950:Melanoma-Specific Antigens; D050778:NFATC Transcription Factors; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018808:Transcription Factor AP-1; D014157:Transcription Factors