title: Effects of the histone deacetylase inhibitor trichostatin A on nuclear texture and c-jun gene expression in drug-sensitive and drug-resistant human H69 lung carcinoma cells.
abstract: BACKGROUND
  Texture analysis of chromatin patterns by image cytometry can be used in the development and refinement of diagnosis and prognosis of cancers and in the follow-up of therapies. However, little is known about the biological mechanisms underlying these patterns. Epigenetic mechanisms as histone posttranslational modifications and particularly histone acetylation could play a major role in the determination of these chromatin patterns and then influence nuclear texture measurements.
  
  
  METHODS
  This study examined the consequences of treatment by the histone deacetylase inhibitor trichostatin A (TSA) on the nuclear texture in human cell lines sensitive and resistant to chemotherapy. Small cell lung carcinoma H69 cells and their variant H69-VP, which is resistant to etoposide, were incubated with 100 ng/ml of TSA for 0 to 24 h. Nuclear texture was evaluated by image cytometry and compared with the histone H4 acetylation level measured by western blotting and expression of c-jun gene evaluated by reverse transcription and real-time polymerase chain reaction.
  
  
  RESULTS
  TSA treatment induced an increase in histone H4 acetylation level in both cell lines. However, at the level of chromatin texture, sensitive H69 cells displayed a progressive chromatin decondensation up to 24 h, whereas resistant H69-VP showed rapid (8 h) but transient changes. Similarly, expression of c-jun increased regularly in TSA-treated H69 cells. In H69-VP cells, an increase was also observed up to 12 h followed by a decrease after 24 h of treatment.
  
  
  CONCLUSIONS
  Analysis of nuclear texture appeared to be a sensitive technique to detect chromatin pattern alterations induced by the histone deacetylase inhibitor TSA in the H69 cell line and enabled the observation of chromatin pattern discrepancies between chemotherapeutic drug-sensitive and drug-resistant cells during this treatment. When c-jun gene expression was analyzed as gene sensitive to epigenetic control, these textural differences seemed to be correlated to gene expression.
authors.affiliation: Unité MéDIAN-CNRS UMR 6142, IFR 53, Faculté de Pharmacie, Reims, France.
authors.forename: Victoria
authors.initials: V
authors.lastname: El-Khoury
authors.forename: Dennis
authors.initials: D
authors.lastname: Gomez
authors.forename: Françoise
authors.initials: F
authors.lastname: Liautaud-Roger
authors.forename: Aurélie
authors.initials: A
authors.lastname: Trussardi-Régnier
authors.forename: Jean
authors.initials: J
authors.lastname: Dufer
mesh_terms: D018288:Carcinoma, Small Cell / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic; D015870:Gene Expression / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects*; D006655:Histone Deacetylases / Q000187:drug effects; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D019044:Image Cytometry; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002843:Chromatin; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C012589:trichostatin A; D006655:Histone Deacetylases