CD81, a cell cycle regulator, is a novel target for histone deacetylase inhibition in glioma cells

• Published in: Neurobiology of disease 2007-06, Vol.26 (3), p.671-680
• Main Authors: Gensert, JoAnn M, Baranova, Oxana V, Weinstein, David E, Ratan, Rajiv R
• Format: Article
• Language: English
• Subjects: Acetylation; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; Astrocyte; Brain Neoplasms - enzymology; Brain Neoplasms - genetics; Brain Neoplasms - physiopathology; Butyrates - pharmacology; Butyrates - therapeutic use; Cell Differentiation - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclin-Dependent Kinase Inhibitor p21 - drug effects; Down-Regulation - drug effects; Down-Regulation - physiology; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - physiology; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - physiology; Gene Silencing - drug effects; Gene Silencing - physiology; Genes, cdc - drug effects; Glioma; Glioma - enzymology; Glioma - genetics; Glioma - physiopathology; HDAC; Histone Deacetylase Inhibitors; Histone Deacetylases - metabolism; Hydroxamic Acids - pharmacology; Hydroxamic Acids - therapeutic use; Neurology; Proliferation; Rats; Rats, Inbred F344; Rats, Wistar; RNA Interference; Tetraspanin 28
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2007.03.008

Abstract Recent advances in cancer cell biology have focused on histone deacetylase inhibitors (HDACi’s) because they target pathways critical to the development and progression of disease. In particular, HDACi’s can induce expression of epigenetically silenced genes that promote growth arrest, differentiation and cell death. In glioma cells, one such repressed gene is the tetraspanin CD81, which regulates cytostasis in various cell lines and in astrocytes, the major cellular component of gliomas. Our studies show that HDACi’s, trichostatin and sodium butyrate, promote growth arrest and differentiation with negligible cell death in glioma cells and induce expression of CD81 and cyclin-dependent kinase inhibitor 1A (p21CIP/WAF-1 ), another regulator of cytostasis in astrocytes. Interference RNA knock-down of CD81 abrogates cytostasis promoted by HDAC inhibition indicating that HDACi-induced CD81 is responsible for growth arrest. Induction of CD81 expression through HDAC inhibition is a novel strategy to promote growth arrest in glioma cells.