Identification of the lysyl oxidase gene as target of the antioncogenic transcription factor, IRF-1, and its possible role in tumor suppression.
The transcriptional activator IFN regulatory factor 1 (IRF-1) and its antagonistic repressor IRF-2 are regulators of the IFN system. IRF-1 also manifests tumor suppressive activity, and its inactivation could contribute to the development of human hematopoietic malignancies. Here, we report the identification of the lysyl oxidase gene as a target gene of IRF-1. An IRF response element was identified in the lysyl oxidase gene promoter. We also demonstrate that the transformed phenotype of ras-expressing embryonic fibroblasts with a null mutation in the IRF-1 allele could be suppressed by the expression of the lysyl oxidase cDNA, implicating its potential role in tumor suppression. Thus, the regulation of the lysyl oxidase gene by IRF-1 could contribute to the multistep process of malignant transformation.
Tan
R S
RS
Department of Immunology, Faculty of Medicine, University of Tokyo, Japan.
Taniguchi
T
T
Harada
H
H
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002472:Cell Transformation, Viral / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D005822:Genetic Vectors; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D051379:Mice; D008969:Molecular Sequence Data; D015689:Oncogene Protein p21(ras) / Q000502:physiology; D010641:Phenotype; D010750:Phosphoproteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection; D014410:Tumor Stem Cell Assay
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; C494258:Irf1 protein, mouse; C494230:Irf2 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D008249:Protein-Lysine 6-Oxidase; D015689:Oncogene Protein p21(ras)