Identification of the Lysyl Oxidase Gene as a Target of the Antioncogenic Transcription Factor, IRF-1, and Its Possible Role in Tumor Suppression1

The transcriptional activator IFN regulatory factor 1 (IRF-1) and its antagonistic represser 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 ra.v-expressing embryonic fibroblasts with a null mutation in the IRF-1 alÃ-elecould 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 malig nant transformation.