Carcinogenesis Advance Access published online on October 10, 2003
Carcinogenesis, doi:10.1093/carcin/bgg187
© 2003 by Oxford University Press
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CARCINOGENESIS
1 Laboratory of Radiation Effect, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-Dong, Nowon-Ku, Seoul 139-706, Korea
* Corresponding author. E-mail: yslee{at}kcch.re.kr.
Received 16 April 2003
; revised 16 September 2003
; accepted 24 September 2003
To identify a set of genes involved in the development of radiation-induced tumorigenesis, we used DNA microarrays consisting of 1,176 mouse genes and compared expression profiles of radioresistant cells, designated NIH3T3-R#1 and -R#4. These cells were tumorigenic in a nude mouse grafting system, as compared to the parental NIH3T3 cells. Expressions of MDM2, CDK6 and CDC25B were found to increase more than 3-fold. Entactin protein levels were downregulated in NIH3T3-R#1 and -R#4 cells. Changes in expression genes were confirmed by reverse transcription-PCR or western blotting. When these genes were transfected to NIH3T3 cells, the CDC25B and MDM2 overexpressing NIH3T3 cells showed radioresistance, while CDK6 overexpressing cells did not. In the case of entactin overexpressing NIH3T3-R#1 or R-#4 cells were still radioresistant. Furthermore, the CDC25B and MDM2 overexpressing cells grafted to nude mice, were tumorigenic. NIH3T3-R#1 and R#4 cells showed increased radiation-induced apoptosis, accompanied by faster growth rate, rather than and earlier radiation-induced G2/M phase arrest, suggesting that the radioresistance of NIH3T3-R#1 and R#4 cells was due to faster growth rate, rather than induction of apoptosis. In the case of MDM2 and CDC25B overexpressing cells, similar phenomena, such as increased apoptosis and faster growth rate, were shown. The above results, therefore, demonstrate involvement of CDC25B and MDM2 overexpression in radiation-induced tumorigenesis and provide novel targets for detection of radiation-induced carcinogenesis.
Radiation tumorigenesis, Raioresistance, Microarray, CDC25B, MDM2
Alteration of gene expressions during radiation-induced resistance and tumorigenesis in NIH3T3 cells revealed by cDNA microarrays: Involvement of MDM2 and CDC25B
2 Laboratory of Experimental Pathology, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-Dong, Nowon-Ku, Seoul 139-706, Korea
3 Division of Life Sciences, Kangwon National University College of Natural Sciences, 192-1 Hyoja2-dong, Chuncheon-Si, Kangwon-do, 200-701 Korea
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