Abstract
Bloom syndrome is caused by homozygous mutations in BLM, which encodes a RecQ DNA helicase. Patient-derived cells deficient in BLM helicase activity exhibit genetic instability - apparent cytogenetically as sister chromatid exchanges - and activated DNA damage signaling. In this report, we show that BLM-knockout colorectal cancer cells exhibited endogenous, ATM-dependent double-strand DNA break responses similar to those recently observed in Bloom syndrome patient-derived cells. Xenograft tumors established from BLM-deficient cancer cells were not radiosensitive, but exhibited growth impairment that was comparable to that of wild type tumors treated with a single, high dose of ionizing radiation. These results suggest that pharmacological inhibitors of BLM would have a radiomimetic effect, and that transient inhibition of BLM activity might be a viable strategy for anticancer therapy.
Original language | English (US) |
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Pages (from-to) | 1783-1786 |
Number of pages | 4 |
Journal | Cancer Biology and Therapy |
Volume | 7 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2008 |
Keywords
- ATM
- BLM
- Bloom syndrome
- Cancer therapy
- DNA damage
- Gene targeting
- Ionizing radiation
- Xenografts
ASJC Scopus subject areas
- Molecular Medicine
- Oncology
- Pharmacology
- Cancer Research