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

Biomed Pharmacother. 2007 Aug;61(7):451-4. doi: 10.1016/j.biopha.2007.03.007. Epub 2007 Apr 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Blotting, Western
  • Butyrates / pharmacology*
  • Cell Line, Tumor
  • Decitabine
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Inhibitors / pharmacology*
  • Epigenesis, Genetic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hydroxamic Acids / pharmacology*
  • Lymphoma / drug therapy
  • Lymphoma / pathology
  • Polymerase Chain Reaction
  • Receptors, Glucocorticoid / drug effects*
  • Receptors, Glucocorticoid / metabolism
  • Reverse Transcription / drug effects

Substances

  • Antineoplastic Agents
  • Butyrates
  • Enzyme Inhibitors
  • Hydroxamic Acids
  • Receptors, Glucocorticoid
  • glucocorticoid receptor alpha
  • glucocorticoid receptor beta
  • trichostatin A
  • Decitabine
  • Azacitidine