title: Trichostatin A-induced TGF-beta type II receptor expression in retinoblastoma cell lines.
abstract: OBJECTIVE
  Retinoblastoma, an intraocular malignant tumor of childhood, is caused by a mutation in the retinoblastoma tumor-suppressor gene RB. Retinoblastoma cells are thought to be resistant to transforming growth factor-beta (TGF-beta) because they do not express the TGF-beta type II receptor (TbetaR-II). In several tumor cell lines, trichostatin A (TSA), a potent inhibitor of histone deacetylase, induces expression of the TbetaR-II gene. The objective of the present study was to determine the effects of TSA on TbetaR-II gene expression in retinoblastoma cells.
  
  
  METHODS
  Four retinoblastoma cell lines were transfected with a TbetaR-II promoter-luciferase reporter construct and analyzed for the effect of TSA on TbetaR-II mRNA expression, TbetaR-II promoter activity, transforming growth factor (TGF)-beta-related signal transduction, and cell growth using RT-PCR, Western blot analysis, chromatin immunoprecipitation, luciferase activity assay, and cell viability assays.
  
  
  RESULTS
  TSA treatment induced the expression of TbetaR-II mRNA, activated the TbetaR-II promoter, and inhibited cell growth in the examined retinoblastoma cell lines. It did not restore TGF-beta-related signaling, however.
  
  
  CONCLUSIONS
  These data show that TSA induces the expression of TbetaR-II mRNA and activates the TbetaR-II promoter in retinoblastoma cells. However, TSA treatment alone was insufficient to restore TGF-beta signaling in these cell lines. The inhibitory effect of TSA on cell growth may be unrelated to its effect on TbetaR-II expression.
authors.affiliation: Department of Ocular Cellular Engineering, Yamagata University Faculty of Medicine, Yamagata City, Yamagata, Japan. kasiwagi@med.id.yamagata-u.ac.jp
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kashiwagi
authors.forename: Kuniko
authors.initials: K
authors.lastname: Horie
authors.forename: Chikako
authors.initials: C
authors.lastname: Kanno
authors.forename: Motoko
authors.initials: M
authors.lastname: Inomata
authors.forename: Takashi
authors.initials: T
authors.lastname: Imamura
authors.forename: Mitsuyasu
authors.initials: M
authors.lastname: Kato
authors.forename: Teiko
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Yamashita
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D019572:Retinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012175:Retinoblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051785:Smad Proteins / Q000235:genetics; D014162:Transfection
chemical_list: D017931:DNA Primers; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; C012589:trichostatin A; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II