Journal
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
Volume 77, Issue 3, Pages 858-866Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ijrobp.2009.12.076
Keywords
Non small-cell lung cancer; Radioresistance; cDNA microarray; Tumor protein p53-inducible protein 3 (TP53I3, or PIG3)
Funding
- Korea Ministry of Health, Welfare and Family Affairs [01-PJ3-PG6-01GN12-0001]
- Korea Ministry of Knowledge Economy [KK-0902]
- National Research Council of Science & Technology (NST), Republic of Korea [KK-0902] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Purpose: Despite the widespread use of radiotherapy as a local and regional modality for the treatment of cancer, some non small-cell lung cancers commonly develop resistance to radiation. We thus sought to clarify the molecular mechanisms underlying resistance to radiation. Methods and Materials: We established the radioresistant cell line H460R from radiosensitive parental H460 cells. To identify the radioresistance-related genes, we performed microarray analysis and selected several candidate genes. Results: Clonogenic and MTT assays showed that H460R was 10-fold more resistant to radiation than H460. Microarray analysis indicated that the expression levels of 1,463 genes were altered more than 1.5-fold in H460R compared with parental H460. To evaluate the putative functional role, we selected one interesting gene tumor protein p53-inducible protein 3 (TP53I3), because that this gene was significantly downregulated in radioresistant H460R cells and that it was predicted to link p53-dependent cell death signaling. Interestingly, messenger ribonucleic acid expression of TP53I3 differed in X-ray irradiated H460 and H460R cells, and overexpression of TP53I3 significantly affected the cellular radiosensitivity of H460R cells. Conclusions: These results show that H460R may be useful in searching for candidate genes that are responsible for radioresistance and elucidating the molecular mechanism of radioresistance. (C) 2010 Elsevier Inc.
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