Identification of differential gene expression profiles of radioresistant lung cancer cell line established by fractionated ionizing radiation in vitro.
BACKGROUND
Radiotherapy plays a critical role in the management of non-small cell lung cancer (NSCLC). This study was conducted to identify gene expression profiles of acquired radioresistant NSCLC cell line established by fractionated ionizing radiation (FIR) by cDNA microarray.


METHODS
The human lung adenocarcinoma cell line Anip973 was treated with high energy X-ray to receive 60 Gy in 4 Gy fractions. The radiosensitivity of Anip973R and its parental line were measured by clonogenic assay. Gene expression profiles of Anip973R and its parental line were analyzed using cDNA microarray consisting of 21 522 human genes. Identified partly different expressive genes were validated by quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR).


RESULTS
Fifty-nine upregulated and 43 downregulated genes were identified to radio-resistant Anip973R. Up-regulated genes were associated with DNA damage repair (DDB2), extracellular matrix (LOX), cell adhesion (CDH2), and apoptosis (CRYAB). Down-regulated genes were associated with angiogenesis (GBP-1), immune response (CD83), and calcium signaling pathway (TNNC1). Subsequent validation of selected eleven genes (CD24, DDB2, IGFBP3, LOX, CDH2, CRYAB, PROCR, ANXA1 DCN, GBP-1 and CD83) by Q-RT-PCR was consistent with microarray analysis.


CONCLUSIONS
Fractionated ionizing radiation can lead to the development of radiation resistance. Altered gene profiles of radioresistant cell line may provide new insights into mechanisms underlying clinical radioresistance for NSCLC.
Xu
Qing-yong
QY
Department of Radiation Oncology, Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, China.
Gao
Yuan
Y
Liu
Yan
Y
Yang
Wei-zhi
WZ
Xu
Xiang-ying
XY
D000230:Adenocarcinoma / Q000235:genetics / Q000532:radiotherapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000532:radiotherapy; D045744:Cell Line, Tumor / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D020411:Oligonucleotide Array Sequence Analysis; D011836:Radiation Tolerance; D020133:Reverse Transcriptase Polymerase Chain Reaction