Oncogenic H-Ras up-regulates expression of Ku80 to protect cells from gamma-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 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.
Chang
In-Youb
IY
Research Center for Proteineous Materials and Department of Pharmacology, School of Medicine, Chosun University, Gwangju, Korea.
Youn
Cha-Kyung
CK
Kim
Hong-Beum
HB
Kim
Mi-Hwa
MH
Cho
Hyun-Ju
HJ
Yoon
Young
Y
Lee
Yun-Sil
YS
Chung
Myung-Hee
MH
You
Ho Jin
HJ
D000818:Animals; D034961:Antigens, Nuclear / Q000096:biosynthesis* / Q000235:genetics; D002470:Cell Survival / Q000502:physiology / Q000528:radiation effects; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D004441:Ecdysterone / Q000031:analogs & derivatives; D005720:Gamma Rays; D005786:Gene Expression Regulation; D011905:Genes, ras / Q000502:physiology*; D000072200:Ku Autoantigen; D051379:Mice; D041681:NIH 3T3 Cells; D020411:Oligonucleotide Array Sequence Analysis; D011836:Radiation Tolerance / Q000502:physiology*; D015854:Up-Regulation; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D004441:Ecdysterone; C008999:ponasterone A; D004247:DNA; C000606510:Xrcc6 protein, mouse; D018631:ras Proteins; D000072200:Ku Autoantigen