Exp Mol Med.  2011 Jul;43(7):419-426. 10.3858/emm.2011.43.7.046.

Time-course analysis of DNA damage response-related genes after in vitro radiation in H460 and H1229 lung cancer cell lines

• Kim KH
• Yoo HY
• Joo KM
• Jung Y
• Jin J
• Kim Y
• Yoon SJ
• Choi SH
• Seol HJ
• Park WY
• Nam DH

• KMID: 1015461
• DOI: http://doi.org/10.3858/emm.2011.43.7.046

Abstract

Radiation is the most useful treatment modality for cancer patients. It initiates a series of signal cascades such as DNA damage response (DDR) signaling for repairing damaged DNA, arresting the cell cycle, and inducing cell death. Until now, few genes have been found to be regulated by radiation, which explains the molecular mechanisms of cellular responses to radiation. Although the transcriptional changes caused by radiation have been widely investigated, little is known about the direct evidence for the transcriptional control of DDR-related genes. Here, we examined the radiosensitivity of two non-small cell lung cancer cell lines (H460 and H1299), which have different p53 status. We monitored the time-dependent changes of 24 DDR-related gene expressions via microarray analysis. Based on the basal expression levels and temporal patterns, we further classified 24 DDR-related genes into four subgroups. Then, we also addressed the protein levels of several DDR-related genes such as TopBP1, Chk1 and Chk2, confirming the results of microarray analysis. Together, these results indicate that the expression patterns of DDR-related genes are associated with radiosensitivity and with the p53 statuses of H460 and H1299, which adds to the understanding of the complex biological responses to radiation.

Keyword

carcinoma, non-small-cell lung; DNA damage; gene expression profiling; microarray analysis; radiation; tumor suppressor protein p53

MeSH Terms

Adaptor Proteins, Signal Transducing/genetics
Cell Cycle Proteins/genetics
Cell Line, Tumor
Cell Survival/radiation effects
DNA Damage/*radiation effects
DNA Repair Enzymes/genetics
DNA-Binding Proteins/genetics
Gene Expression Profiling
Gene Expression Regulation, Neoplastic/*radiation effects
Humans
Lung Neoplasms
Radiation Tolerance/genetics
Signal Transduction