Time-course analysis of DNA damage response-related genes afterin vitroradiation in H460 and H1229 lung cancer cell lines

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.

Transcriptional-mediated effects of radiation on the expression of immune susceptibility markers in melanoma

“…Nearly all of the targets with patterns of expression that deviated from this trend ( Bax, Puma, Mdm2 , and others) were genes involved in the DNA damage response (Supplementary Fig. 4B), which was consistent with expected patterns of rapid transcriptional upregulation of this machinery at 24–72 hours after RT [17–18]. Changes in gene expression for these markers peaked at the earliest measured time point, collected 2.5 days (60 hours) following RT.…”

SIRT1 Pathway Dysregulation in the Smoke-Exposed Airway Epithelium and Lung Tumor Tissue

“…The ATM pathway signature was tested using GSE20549 and ATM pathway activation increased in H1299 cells and transiently decreased and then restored in H460 cells (Supplemental Figure 2A). The pattern of ATM pathway activation is mirrored by the expression levels of MRE11A, ATM, ATR, p53BP1, CHK2, TOPBP1, CDC7, Claspin and CDC25C measured by Kim et al (37) demonstrating our genomic ATM profile accurately predicts ATM activity in this study. The GPX1 pathway signature was tested using GSE23895 and GPX1 pathway activation, as measured by the genomic profile for GPX1, decreased in the liver of rats fed selenium deficient diets and was highly correlated with GPX1 activity measured in the liver (Supplemental Figure 2 B) (38)).…”

Eye-specific gene expression following embryonic ethanol exposure in zebrafish: Roles for heat shock factor 1

“…Previous studies in mouse whole embryo and fetal brain tissue [5, 28-32] using a single time point microarray approach yielded a set of genes (and micro-RNAs) with diverse biological functions differentially expressed in ethanol-treated animals. The time series microarray approach is becoming an increasingly popular method for gene expression studies, particularly during development [33], tissue regeneration [34], in response to environmental stressors [35], in applications for which independent sampling schemes are used [36] and when sample numbers are limited [37, 38]. …”