Oncogenic H-ras Up-regulates expression of Ku80 to protect cells from γ-ray irradiation in NIH3T3 cells

The Ras activation contributes to radioresistance, but the mechanism is unclear. This article shows that the expression of the dominant-positive H-Ras increased the Ku80 level, which is one of the key enzymes involved in repairing dsDNA breaks (DSB). After exposing the cells to ionizing radiation an...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2005-08, Vol.65 (15), p.6811-6819
Main Authors: CHANG, In-Youb, YOUN, Cha-Kyung, KIM, Hong-Beum, KIM, Mi-Hwa, CHO, Hyun-Ju, YOON, Young, LEE, Yun-Sil, CHUNG, Myung-Hee, HO JIN YOU
Format: Article
Language:English
Subjects:
Animals
Antigens, Nuclear - biosynthesis
Antigens, Nuclear - genetics
Antineoplastic agents
Biological and medical sciences
Cell Survival - physiology
Cell Survival - radiation effects
DNA - metabolism
DNA - radiation effects
DNA Damage
DNA Repair - radiation effects
DNA-Binding Proteins - biosynthesis
DNA-Binding Proteins - genetics
Down-Regulation
Ecdysterone - analogs & derivatives
Gamma Rays
Gene Expression Regulation
Genes, ras - physiology
Ku Autoantigen
Medical sciences
Mice
NIH 3T3 Cells
Oligonucleotide Array Sequence Analysis
Pharmacology. Drug treatments
Radiation Tolerance - physiology
ras Proteins - biosynthesis
ras Proteins - genetics
Tumors
Up-Regulation
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Summary:The Ras activation contributes to radioresistance, but the mechanism is unclear. This article shows that the expression of the dominant-positive H-Ras increased the Ku80 level, which is one of the key enzymes involved in repairing dsDNA breaks (DSB). After exposing the cells to ionizing radiation and analyzing them using an electrophoretic mobility shift assay and pulsed-field gel electrophoresis, it was found that activated H-Ras expression in NIH3T3 cells increases the DNA-binding activity of Ku80 and increases the DSB repair activity. Ku80 small interfering RNA expression was shown to reduce the oncogenic H-Ras-mediated increase in the DSBs and suppress the oncogenic H-Ras-mediated resistance of the cells to gamma-ray irradiation, whereas Ku80 overexpression in the NIH3T3 cells significantly increased the radioresistance. These results suggest that the Ku80 expression induced by oncogenic H-Ras seems to play an important role in protecting cells against gamma-ray irradiation.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-04-4065