title: Modulation of interferon action by retinoids. Induction of murine STAT1 gene expression by retinoic acid.
abstract: We have previously demonstrated that up-regulation of STAT1 protein by all-trans-retinoic acid (RA) in interferon (IFN)-unresponsive cells permits growth inhibition by IFNs. Here, we show that the promoter of STAT1 directly responds to retinoic acid treatment. Sequence and functional analysis of the murine STAT1 promoter have identified a direct repeat motif that serves as a retinoic acid response element. Mutagenesis of this element resulted in a loss of response to RA. This element is activated by RA receptors alpha, beta, and gamma. In vivo, RA receptor beta and retinoid X receptor alpha preferentially interacted with this element. Thus, these data define a molecular basis for the synergy between IFNs and retinoids in tumor growth inhibition.
authors.affiliation: University of Maryland Cancer Center, Department of Microbiology & Immunology, Program in Oncology, Molecular and Cellular Biology Program, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: V
authors.initials: V
authors.lastname: Kolla
authors.forename: X
authors.initials: X
authors.lastname: Weihua
authors.forename: D V
authors.initials: DV
authors.lastname: Kalvakolanu
mesh_terms: D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014212:Tretinoin; D007371:Interferon-gamma