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.
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.
Authors: Tanya M Tekautz; Christine E Fuller; Susan Blaney; Maryam Fouladi; Alberto Broniscer; Thomas E Merchant; Matthew Krasin; James Dalton; Gregory Hale; Larry E Kun; Dana Wallace; Richard J Gilbertson; Amar Gajjar Journal: J Clin Oncol Date: 2005-03-01 Impact factor: 44.544
Authors: Jaclyn A Biegel; Lu Tan; Fan Zhang; Luanne Wainwright; Pierre Russo; Lucy B Rorke Journal: Clin Cancer Res Date: 2002-11 Impact factor: 12.531
Authors: David B Seligson; Steve Horvath; Tao Shi; Hong Yu; Sheila Tze; Michael Grunstein; Siavash K Kurdistani Journal: Nature Date: 2005-06-30 Impact factor: 49.962
Authors: Joanne M Hilden; Sharon Meerbaum; Peter Burger; Jonathan Finlay; Anna Janss; Bernd W Scheithauer; Andrew W Walter; Lucy B Rorke; Jaclyn A Biegel Journal: J Clin Oncol Date: 2004-07-15 Impact factor: 44.544
Authors: Roger J Packer; Jaclyn A Biegel; Susan Blaney; Jonathan Finlay; J Russell Geyer; Richard Heideman; Joanne Hilden; Anna J Janss; Larry Kun; Gilbert Vezina; Lucy B Rorke; Malcolm Smith Journal: J Pediatr Hematol Oncol Date: 2002 Jun-Jul Impact factor: 1.289
Authors: Steven M Pollard; Koichi Yoshikawa; Ian D Clarke; Davide Danovi; Stefan Stricker; Roslin Russell; Jane Bayani; Renee Head; Marco Lee; Mark Bernstein; Jeremy A Squire; Austin Smith; Peter Dirks Journal: Cell Stem Cell Date: 2009-06-05 Impact factor: 24.633
Authors: Susan N Chi; Mary Ann Zimmerman; Xiaopan Yao; Kenneth J Cohen; Peter Burger; Jaclyn A Biegel; Lucy B Rorke-Adams; Michael J Fisher; Anna Janss; Claire Mazewski; Stewart Goldman; Peter E Manley; Daniel C Bowers; Anne Bendel; Joshua Rubin; Christopher D Turner; Karen J Marcus; Liliana Goumnerova; Nicole J Ullrich; Mark W Kieran Journal: J Clin Oncol Date: 2008-12-08 Impact factor: 44.544
Authors: Eric H Raabe; Jeffrey A Rubens; Sabrina Z Wang; Brad Poore; Jesse Alt; Antoinette Price; Sariah J Allen; Allison R Hanaford; Harpreet Kaur; Brent A Orr; Barbara S Slusher; Charles G Eberhart Journal: Clin Cancer Res Date: 2019-07-12 Impact factor: 12.531
Authors: Jasmina Makarević; Nassim Tawanaie; Eva Juengel; Michael Reiter; Jens Mani; Igor Tsaur; Georg Bartsch; Axel Haferkamp; Roman A Blaheta Journal: J Cell Mol Med Date: 2014-04-30 Impact factor: 5.310