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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
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
Zeitschrift
Cancer Research
Quellenangaben
Band: 73,
Heft: 14,
Seiten: 4247-4255
Verlag
American Association for Cancer Research (AACR)
Verlagsort
Philadelphia, Pa.
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Radiation Biology (ISB)