D York1, C D Sproul2, N Chikere2, P J Dickinson1, J M Angelastro2. 1. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California. 2. Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California.
Abstract
BACKGROUND: Activating transcription factor 5 (ATF5) is a transcription factor that is highly expressed in undifferentiated neural progenitor/stem cells as well as a variety of human cancers including gliomas. AIMS: In this study, we examined the expression and localization of ATF5 protein in canine gliomas, and targeting of ATF5 function in canine glioma cell lines. MATERIALS AND METHODS: Paraffin-embedded canine brain glioma tissue sections and western blots of tumours and glioma cells were immunoassayed with anti-ATF5 antibody. Viability of glioma cells was tested with a synthetic cell-penetrating ATF5 peptide (CP-d/n ATF5) ATF5 antagonist. RESULTS: ATF5 protein expression was in the nucleus and cytoplasm and was present in normal adult brain and tumour samples, with significantly higher expression in tumours as shown by western immunoblotting. CP-d/n ATF5 was found to decrease cell viability in canine glioma cell lines in vitro in a dose-dependent manner. CONCLUSION: Similarities in expression of ATF5 in rodent, dog and human tumours, and cross species efficacy of the CP-d/n ATF5 peptide support the development of this ATF5-targeting approach as a novel and translational therapy in dog gliomas.
BACKGROUND:Activating transcription factor 5 (ATF5) is a transcription factor that is highly expressed in undifferentiated neural progenitor/stem cells as well as a variety of humancancers including gliomas. AIMS: In this study, we examined the expression and localization of ATF5 protein in caninegliomas, and targeting of ATF5 function in canineglioma cell lines. MATERIALS AND METHODS:Paraffin-embedded canine brain glioma tissue sections and western blots of tumours and glioma cells were immunoassayed with anti-ATF5 antibody. Viability of glioma cells was tested with a synthetic cell-penetrating ATF5 peptide (CP-d/nATF5) ATF5 antagonist. RESULTS:ATF5 protein expression was in the nucleus and cytoplasm and was present in normal adult brain and tumour samples, with significantly higher expression in tumours as shown by western immunoblotting. CP-d/nATF5 was found to decrease cell viability in canineglioma cell lines in vitro in a dose-dependent manner. CONCLUSION: Similarities in expression of ATF5 in rodent, dog and humantumours, and cross species efficacy of the CP-d/nATF5 peptide support the development of this ATF5-targeting approach as a novel and translational therapy in doggliomas.
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