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González-Vasconcellos, I.M. ; Anastasov, N. ; Sanli-Bonazzi, B. ; Klymenko, O. ; Atkinson, M.J. ; Rosemann, M.

Rb1 haploinsufficiency promotes telomere attrition and radiation-induced genomic instability.

Cancer Res. 73, 4247-4255 (2013)
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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
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 0008-5472
e-ISSN 1538-7445
Zeitschrift Cancer Research
Quellenangaben Band: 73, Heft: 14, Seiten: 4247-4255 Artikelnummer: , Supplement: ,
Verlag American Association for Cancer Research (AACR)
Verlagsort Philadelphia, Pa.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Biology (ISB)
POF Topic(s) 30202 - Environmental Health
Forschungsfeld(er) Radiation Sciences
PSP-Element(e) G-500200-001
PubMed ID 23687339
DOI 10.1158/0008-5472.CAN-12-3117
WOS ID WOS:000321823600009
Scopus ID 84880914664
Erfassungsdatum 2013-06-24
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