Anti-Oncogenic and Oncogenic Potentials of Interferon Regulatory Factors-1 and -2

Abstract

Interferon regulatory factor-1 (IRF-1), a transcriptional activator, and IRF-2, its antagonistic repressor, have been identified as regulators of type I interferon and interferon-inducible genes. The IRF-1 gene is itself interferon-inducible and hence may be one of the target genes critical for interferon action. When the IRF-2 gene was overexpressed in NIH 3T3 cells, the cells became transformed and displayed enhanced tumorigenicity in nude mice. This transformed phenotype was reversed by concomitant overexpression of the IRF-1 gene. Thus, restrained cell growth depends on a balance between these two mutually antagonistic transcription factors.

Cooperative activity between HER oncogenes and the tumor suppressor IRF-1 results in apoptosis

“…Moreover, transformation mediated by the EGFR derivates HER1 and HER2, a common feature of human tumor cells (Garcia et al, 1997), is also inhibited. Previously, it was shown that IRF-1 can suppress cellular transformation induced by di erent oncogenes, such as myc, fosB (Tanaka et al, 1994b) and IRF-2 (Harada et al, 1993;Futaki et al, 1996). Thus, our results, together with earlier reports, support the de®nition of IRF-1 as a tumor suppressor protein.…”

MyD genes in negative growth control

“…Consistent with this notion, Harada et al (1993) have shown that balanced expression of IRF-1 and IRF-2, an antagonistic repressor of IRF-1 and IFNb transcription, is critical for normal cell growth. Overexpression of IRF-2 in NIH3T3 cells resulted in transformation and enhanced tumorigenicity of the cells in nude mice, whereas simultaneous overexpression of IRF-1 and IRF-2 reverted this transformed phenotype.…”

Interferon regulatory factor-2 in orange-spotted grouper (Epinephelus coioides): Gene, inductive expression pattern and subcellular localization

“…IRF-2 exhibits both transcriptional activating and repressing activities (Shi et al, 1991). IRF-2 is a critical transacting factor that regulates in vivo responses to LPS and is a potential oncogene (Harada et al, 1993). IRF-2 also has an unexpected role in the regulation of apoptosis and cell growth (Cuesta et al, 2003).…”