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Open Access Green as soon as Postprint is submitted to ZB.
Rb1 haploinsufficiency promotes telomere attrition and radiation-induced genomic instability.
Cancer Res. 73, 4247-4255 (2013)
Germ-line mutations of the retinoblastoma gene (RB1) predispose to both sporadic and radiation-induced osteosarcoma, tumors characterized by high levels of genomic instability and activation of ALT (alternative lengthening of telomeres). Mice with haploinsufficiency of the Rb1 gene in the osteoblastic lineage reiterate the radiation-susceptibility to osteosarcoma seen in patients with germ-line RB1 mutations. We demonstrate that the susceptibility is accompanied by an increase in genomic instability resulting from Rb1-dependent telomere erosion. Radiation exposure did not accelerate the rate of telomere loss but amplified the genomic instability resulting from the dysfunctional telomeres. We propose that telomere maintenance is a non-canonical caretaker function of Rb1, and that a deficiency of Rb1 increases susceptibility to radiation-induced carcinogenesis by promoting chromosomal aberrations.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Micronucleus; Cre recombinase; Radiation carcinogenesis; Secondary osteosarcoma; Osteoblast; Lentivirus; RNA interference; Mutant Mice ; Rb ; Retinoblastoma ; Expression ; Cancer ; Tumors ; Cells ; Predisposition ; Dysfunction ; Osteoblast
ISSN (print) / ISBN
0008-5472
e-ISSN
1538-7445
Journal
Cancer Research
Quellenangaben
Volume: 73,
Issue: 14,
Pages: 4247-4255
Publisher
American Association for Cancer Research (AACR)
Publishing Place
Philadelphia, Pa.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Radiation Biology (ISB)