Abstract
Promyelocytic leukemia zinc-finger (PLZF) is a transcriptional repressor and tumor suppressor. PLZF is expressed in melanocytes but not in melanoma cells, and recovery of PLZF expression markedly suppresses melanoma cell growth. Several target genes regulated by PLZF have been identified, but the precise function of PLZF remains uncertain. Here, we searched for candidate target genes of PLZF by DNA microarray analysis. Pre-B-cell leukemia transcription factor 1 (Pbx1) was one of the prominently suppressed genes. Pbx1 was highly expressed in melanoma cells, and its expression was reduced by transduction with the PLZF gene. Moreover, the growth suppression mediated by PLZF was reversed by enforced expression of Pbx1. Knockdown of Pbx1 by specific small interfering RNAs suppressed melanoma cell growth. We also found that Pbx1 binds HoxB7. Reverse transcription-polymerase chain reaction analysis demonstrated that repression of Pbx1 by PLZF reduces the expression of HoxB7 target genes, including tumor-associated neoangiogenesis factors such as basic fibroblast growth factor, angiopoietin-2 and matrix metalloprotease 9. These findings suggest that deregulation of Pbx1 expression owing to loss of PLZF expression contributes to the progression and/or pathogenesis of melanoma.
MeSH terms
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Angiopoietin-2 / genetics
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Angiopoietin-2 / metabolism
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Blotting, Western
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Cell Proliferation
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / metabolism
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Down-Regulation
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Electrophoretic Mobility Shift Assay
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Fibroblast Growth Factor 2 / genetics
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Fibroblast Growth Factor 2 / metabolism
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Gene Expression Regulation, Neoplastic
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Immunoprecipitation
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Kruppel-Like Transcription Factors
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Matrix Metalloproteinase 9 / genetics
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Matrix Metalloproteinase 9 / metabolism
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Melanocytes / metabolism
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Melanoma / genetics
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Melanoma / pathology*
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Oligonucleotide Array Sequence Analysis
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Pre-B-Cell Leukemia Transcription Factor 1
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Promoter Regions, Genetic / genetics
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Promyelocytic Leukemia Zinc Finger Protein
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transcription, Genetic
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Tumor Cells, Cultured
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Zinc Fingers
Substances
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Angiopoietin-2
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DNA-Binding Proteins
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HOXB7 protein, human
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Homeodomain Proteins
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Kruppel-Like Transcription Factors
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Pre-B-Cell Leukemia Transcription Factor 1
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Promyelocytic Leukemia Zinc Finger Protein
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Repressor Proteins
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Transcription Factors
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PBX1 protein, human
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Fibroblast Growth Factor 2
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ZBTB16 protein, human
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Matrix Metalloproteinase 9