title: Epigenetic modification after inhibition of IGF-1R signaling in human central nervous system atypical teratoid rhabdoid tumor (AT/RT).
abstract: OBJECTIVE
  This study investigated epigenetic modifications in human central nervous system atypical teratoid rhabdoid tumors (AT/RTs), in response to inhibition of insulin-like growth factor receptor 1 (IGF-1R).
  
  
  METHODS
  Tumor tissue was obtained from two pediatric patients, tissue was dissociated, and primary cultures were established. Cultured cells were treated with picropodophyllin (PPP; 0, 1, and 2 μM for 48 h), a selective IGF-1R inhibitor. Histone acetylation and methylation patterns (H3K9ac, H3K18ac, H3K4me3, H3K27me3) and levels of histone deacetylases (HDACs; HDAC1, HDAC3, and SirT1) and histone acetyl transferases (GCN5 and p300) were examined. H3K9ac and H3K18ac decreased in response to treatment with PPP. HDAC levels showed a biphasic response, increasing with 1 μM PPP, but then decreasing with 2 μM PPP.
  
  
  CONCLUSIONS
  Inhibition of IGF-1R modified epigenetic status in AT/RT. Determining the mechanisms behind these modifications will guide the development of novel therapeutic targets for this malignant embryonal cancer.
authors.affiliation: Pediatric Neurosurgery Research Lab, Developmental Biology Program, Division of Pediatric Neurosurgery, Children's Hospital of Chicago Research Center and Department of Neurosurgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA.
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Shim
authors.forename: Guifa
authors.initials: G
authors.lastname: Xi
authors.forename: Barbara-Mania
authors.initials: BM
authors.lastname: Farnell
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Takao
authors.initials: T
authors.lastname: Tsurubuchi
authors.forename: Tadanori
authors.initials: T
authors.lastname: Tomita
authors.forename: C Shekhar
authors.initials: CS
authors.lastname: Mayanil
mesh_terms: D000107:Acetylation / Q000187:drug effects; D016543:Central Nervous System Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000502:physiology*; D057890:Epigenomics; D051548:Histone Acetyltransferases / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation / Q000187:drug effects; D011034:Podophyllotoxin / Q000031:analogs & derivatives / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018335:Rhabdoid Tumor / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D013724:Teratoma / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D006657:Histones; C415032:picropodophyllin; D051548:Histone Acetyltransferases; D017526:Receptor, IGF Type 1; D006655:Histone Deacetylases; D011034:Podophyllotoxin