Child's Nervous System

, Volume 29, Issue 8, pp 1245–1251

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
Original Paper

DOI: 10.1007/s00381-013-2087-7

Cite this article as:
Shim, KW., Xi, G., Farnell, BM. et al. Childs Nerv Syst (2013) 29: 1245. doi:10.1007/s00381-013-2087-7

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.

Keywords

Epigenetic modificationAtypical teratoid rhabdoid tumorHistone deacetylaseHistone acetyl transferaseIGF-1RPicropodophyllin

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Kyu-Won Shim
    • 1
    • 2
  • Guifa Xi
    • 1
  • Barbara-Mania Farnell
    • 4
  • Dong-Seok Kim
    • 2
  • Takao Tsurubuchi
    • 1
    • 3
  • Tadanori Tomita
    • 1
    • 5
    • 6
  • C. Shekhar Mayanil
    • 1
    • 5
    • 6
  1. 1.Pediatric Neurosurgery Research Lab, Developmental Biology Program, Division of Pediatric NeurosurgeryChildren’s Hospital of Chicago Research Center and Department of Neurosurgery, Northwestern University Feinberg School of MedicineChicagoUSA
  2. 2.Department of Pediatric Neurosurgery, Severance Children’s HospitalYonsei University College of MedicineSeoulSouth Korea
  3. 3.Department of Neurosurgery, Graduate School of Comprehensive Human SciencesUniversity of TsukubaTsukubaJapan
  4. 4.Department of BiologyPurdue University CalumetHammondUSA
  5. 5.Developmental Biology Program, Division of Pediatric Neurosurgery, Falk Brain Tumor CenterAnn & Robert H. Lurie Children’s Hospital of Chicago and Department of Neurosurgery, Northwestern University Feinberg School of MedicineChicagoUSA
  6. 6.Pediatric Neurosurgery Research Lab, Developmental Biology Program, Division of Pediatric Neurosurgery Department of NeurosurgeryNorthwestern University Feinberg School of MedicineChicagoUSA