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Oncotarget. 2012 Aug;3(8):774-82.

Mutant IDH1 is required for IDH1 mutated tumor cell growth.

Author information

1
The Preston Robert Tisch Brain Tumor Center, The Pediatric Brain Tumor Foundation Institute, and The Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.

Abstract

Frequent somatic hotspot mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in gliomas, acute myeloid leukemias, chondrosarcomas, and other cancers, providing a likely avenue for targeted cancer therapy. However, whether mutant IDH1 protein is required for maintaining IDH1 mutated tumor cell growth remains unknown. Here, using a genetically engineered inducible system, we report that selective suppression of endogenous mutant IDH1 expression in HT1080, a fibrosarcoma cell line with a native IDH1(R132C) heterozygous mutation, significantly inhibits cell proliferation and decreases clonogenic potential. Our findings offer insights into changes that may contribute to the inhibition of cell proliferation and offer a strong preclinical rationale for utilizing mutant IDH1 as a valid therapeutic target.

PMID:
22885298
PMCID:
PMC3478455
DOI:
10.18632/oncotarget.577
[Indexed for MEDLINE]
Free PMC Article

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