Differential gene expression profiles of radioresistant non-small-cell lung cancer cell lines established by fractionated irradiation: tumor protein p53-inducible protein 3 confers sensitivity to ionizing radiation.
OBJECTIVE
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
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.
Toxicogenomics Team, Korea Institute of Toxicology, Daejeon, South Korea.
Young Sook
YS
Lee
Jung-Hwa
JH
Oh
Seokjoo
S
Yoon
Myung-Sang
MS
Kwon
Chang-Woo
CW
Song
Ki-Hwan
KH
Kim
Moon-June
MJ
Cho
Mohamad Lalmodin
ML
Mollah
Young Jin
YJ
Je
Yoon-Dong
YD
Kim
Chang Deok
CD
Kim
Jeung-Hoon
JH
Lee
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics*
D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; C411296:TP53I3 protein, human