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

Shim, K. W.; Xi, G.; Farnell, B. M.; Kim, D. S.; Tsurubuchi, T.; Tomita, T.; Mayanil, C. S.

Childs Nerv Syst. 2013 Apr 30; 29(8):1245-51

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 muM 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 muM PPP, but then decreasing with 2 muM 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.

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