Enhanced adenovirus transgene expression in malignant cells treated with the histone deacetylase inhibitor FR901228.
The presence of coxsackie and adenovirus receptor (CAR) and alpha(v) integrin on cell surfaces is required for efficient adenovirus infection. Treatment of cells with the histone deacetylase inhibitor FR901228 (depsipeptide) increased CAR and alpha(v) integrin RNA levels in six cancer cell lines. Sodium butyrate and trichostatin A, other histone deacetylase inhibitors, caused similar increases. Cells treated with FR901228 prior to infection had a 4-10-fold increase in transgene expression from a beta-galactosidase-expressing adenoviral vector. These studies suggest that FR901228 increases the efficiency of adenoviral transgene expression and may be useful in cancer gene therapy.
Kitazono
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Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Goldsmith
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ME
Aikou
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T
Bates
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Fojo
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D000256:Adenoviridae / Q000235:genetics*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D047630:Depsipeptides; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D039564:Integrin alphaV; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy / Q000821:virology; D010456:Peptides, Cyclic; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D011991:Receptors, Virus / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D015703:Antigens, CD; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D047630:Depsipeptides; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D039564:Integrin alphaV; D010456:Peptides, Cyclic; D012334:RNA, Neoplasm; D011991:Receptors, Virus; C087123:romidepsin