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.
Lee
Young Sook
YS
Toxicogenomics Team, Korea Institute of Toxicology, Daejeon, South Korea.
Oh
Jung-Hwa
JH
Yoon
Seokjoo
S
Kwon
Myung-Sang
MS
Song
Chang-Woo
CW
Kim
Ki-Hwan
KH
Cho
Moon-June
MJ
Mollah
Mohamad Lalmodin
ML
Je
Young Jin
YJ
Kim
Yoon-Dong
YD
Kim
Chang Deok
CD
Lee
Jeung-Hoon
JH
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