Trichostatin A, sodium butyrate, and 5-aza-2'-deoxycytidine alter the expression of glucocorticoid receptor alpha and beta isoforms in Hut-78 T- and Raji B-lymphoma cell lines.
The glucocorticoid receptor (GR) is mainly expressed as nine-exon alternatively spliced variants, encoding functional GRalpha and nonfunctional GRbeta. Overexpression of GRbeta splice variant was found in glucocorticoid-resistant patients with some autoimmune diseases and hematological malignancies. Employing reverse transcription, real-time quantitative PCR, and western blot analysis, we determined an effect of trichostatin A (TSA), sodium butyrate (NaBu) and 5-aza-2'-deoxycytidine (5-dAzaC) on GRalpha and GRbeta expression in Hut-78 T- and Raji B-lymphoma cell lines. We found that TSA, NaBu, and 5-dAzaC significantly increase the expression of GRalpha transcript and protein, whereas GRbeta transcript and protein expression was profoundly decreased in Hut-78 T- and Raji B- lymphoma cell lines. Our observation suggests that changes of epigenetic milieu inside cells may alter the expression of GRalpha and GRbeta isoforms.
Piotrowska
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Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences, 6 Swiecickiego St., 60-781 Poznan, Poland.
Jagodzinski
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PP
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000077209:Decitabine; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008223:Lymphoma / Q000188:drug therapy / Q000473:pathology; D016133:Polymerase Chain Reaction; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D048348:Reverse Transcription / Q000187:drug effects
D000970:Antineoplastic Agents; D002087:Butyrates; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine