Elevated and Deregulated Expression of HDAC3 in Human Astrocytic Glial Tumours

Libý, P.; Kostrouchová, M.; Pohludka, M.; Yilma, P.; Hrabal, P.; Sikora, J.; Brožová, E.; Kostrouchová, M.; Rall, J. E.; Kostrouch, Zdeněk

doi:10.14712/fb2006052010021

Fol. Biol. 2006, 52, 21-33

https://doi.org/10.14712/fb2006052010021

Elevated and Deregulated Expression of HDAC3 in Human Astrocytic Glial Tumours

P. Libý¹, M. Kostrouchová¹, M. Pohludka¹, P. Yilma¹, P. Hrabal², J. Sikora³, E. Brožová⁴, M. Kostrouchová⁴, J. E. Rall⁵, Zdeněk Kostrouch¹

¹Laboratory of Molecular Pathology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
²Department of Pathology, Central Military Hospital Střešovice, Prague, Czech Republic
³Institute of Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
⁴Laboratory of Molecular Biology and Genetics, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
⁵National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

Received May 2006
Accepted May 2006

Abnormal expression of histone deacetylases may contribute to the establishment of a cancer specific transcription profile. We examined expression of HDAC3 in human non-malignant gliosis and glial astrocytic tumours. Samples from four non-malignant gliosis and 17 astrocytic gliomas (six of grade II, one of grade III and ten of grade IV) removed for therapeutic purposes were assayed for HDAC3 expression at mRNA and protein levels. HDAC3 mRNA was detected in nontumorous gliosis as well as in all examined glial tumours. Seven out of eleven examined high-grade tumours showed an elevated number of copies of HDAC3 mRNA. Western blot analysis detected high levels of expression of HDAC3 in the majority of the examined tumours. Immunohistochemistry and immunofluorescence made on a collection of 35 astrocytic tumours detected nuclear as well as cytoplasmic HDAC3 expression in all of those tumours. While the distribution of HDAC3 was both nuclear as well as cytoplasmic and moderate in intensity in non-malignant tissues and low-grade gliomas, high-grade tumours expressed HDAC3 in a focally deregulated pattern that included strongly pronounced cytoplasmic localization. Confocal microscopy and additional co-localization analysis detected nuclear HDAC3 in all tumours examined. We conclude that HDAC3 expression is elevated in human astrocytic tumours and its expression pattern is deregulated at the cellular level in high-grade gliomas.