Epigenetic modification after inhibition of IGF-1R signaling in human central nervous system atypical teratoid rhabdoid tumor (AT/RT)

Kyu Won Shim, Guifa Xi, Barbara Mania Farnell, Dong Seok Kim, Takao Tsurubuchi, Tadanori Tomita*, C. Shekhar Mayanil

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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). Materials and 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1245-1251
Number of pages7
JournalChild's Nervous System
Volume29
Issue number8
DOIs
StatePublished - Aug 1 2013

Keywords

  • Atypical teratoid rhabdoid tumor
  • Epigenetic modification
  • Histone acetyl transferase
  • Histone deacetylase
  • IGF-1R
  • Picropodophyllin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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