Ku70: a candidate tumor suppressor gene for murine T cell lymphoma.
We present evidence that inactivation of the Ku70 gene leads to a propensity for malignant transformation both in vitro and in vivo. In vitro, Ku70-/- mouse fibroblasts displayed an increased rate of sister chromatid exchange and a high frequency of spontaneous neoplastic transformation. In vivo, Ku70-/- mice, known to be defective in B but not T lymphocyte maturation, developed thymic and disseminated T cell lymphomas at a mean age of 6 months with CD4+CD8+ tumor cells. These findings directly demonstrate that Ku70 deficiency facilitates neoplastic growth and suggest a novel role of the Ku70 locus in tumor suppression.
Li
G C
GC
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. g-li@ski.mskcc.org
Ouyang
H
H
Li
X
X
Nagasawa
H
H
Little
J B
JB
Chen
D J
DJ
Ling
C C
CC
Fuks
Z
Z
Cordon-Cardo
C
C
D000818:Animals; D034961:Antigens, Nuclear; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002869:Chromosome Aberrations; D003114:Colony-Forming Units Assay; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects; D005720:Gamma Rays; D016147:Genes, Tumor Suppressor; D006627:Hirschsprung Disease / Q000235:genetics; D000072200:Ku Autoantigen; D016399:Lymphoma, T-Cell / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D016513:Mice, SCID; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D011836:Radiation Tolerance / Q000235:genetics; D012854:Sister Chromatid Exchange; D013601:T-Lymphocytes / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics / Q000473:pathology; D014407:Tumor Cells, Cultured
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen