Alteration of gene expression during radiation-induced resistance and tumorigenesis in NIH3T3 cells revealed by cDNA microarrays: Involvement of MDM2 and CDC25B

Chang Mo Kang, Hye Nyun Cho, Joo Mee Ahn, Seung Sook Lee, Doo Il Jeoung, Chul Koo Cho, Sangwoo Bae, Su Jae Lee, Yun Sil Lee

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

To identify a set of genes involved in the development of radiation-induced tumorigenesis, we used DNA microarrays consisting of 1176 mouse genes and compared expression profiles of radioresistant cells, designated NIH3T3-R1 and NIH3T3-R4. These cells were tumorigenic in a nude mouse grafting system, as compared with the parental NIH3T3 cells. Expression of MDM2, CDK6 and CDC25B was found to increase more than 3-fold. Entactin protein levels were down-regulated in NIH3T3-R1 and NIH3T3-R4 cells. Changes in gene expression were confirmed by reverse transcription-PCR or western blotting. When these genes were transfected into NIH3T3 cells, CDC25B and MDM2 overexpressing NIH3T3 cells showed radio-resistance, while CDK6 overexpressing cells did not. In the case of entactin, overexpressing NIH3T3-R1 and NIH3T3-R4 cells were still radioresistant. Furthermore, CDC25B and MDM2 overexpressing cells grafted into nude mice were tumorigenic. NIH3T3-R1 and NIH3T3-R4 cells showed increased radiation-induced apoptosis accompanied by a faster growth rate, rather than an earlier radiation-induced G2/M phase arrest, suggesting that the radioresistance of NIH3T3-R1 and NIH3T3-R4 cells was due to a faster growth rate rather than induction of apoptosis. In the case of MDM2 and CDC25B overexpressing cells, similar phenomena, such as increased apoptosis and a 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.

Original languageEnglish
Pages (from-to)123-132
Number of pages10
JournalCarcinogenesis
Volume25
Issue number1
DOIs
StatePublished - Jan 2004

Bibliographical note

Funding Information:
This work was supported by the Nuclear R&D Program of the Ministry of Science and Technology of Korea.

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