Differential Gene Expression and Activation of Signaling Pathways in Radioresistant and Radiosensitive Cancer Cell Lines

Abstract

The aim of the investigation was to study differential gene expression and signaling pathways activation in radioresistant and radiosensitive cancer cell lines.Materials and Methods. K562 radioresistant cancer cell line of chronic myeloleukosis, and HCT-116p53 (+/+), HCT-116p53 (-/-), Me45 radiosensitive cancer cell lines were used in the study. Transcriptome analysis was performed using Affymetrix DNA microarray HGU133A series. Original Gene Selector program was used for bioinformation analysis. Protein interaction networks were studied by means of online STRING 9.0 system. To range the genes according to the signaling pathways the PANTHER program and QIAGEN SABiosciences database were used. Quantitative activation of signaling pathways was calculated with the help of OncoFinder bioinformation algorithm.Results. Four genes (DAAM1, IFNAR2, PALLD, STK17A) were identified to increase their expression in radioresistant cell line and to decrease it in radiosensitive cell lines under radiation exposure. Three signal pathways -Wnt, Interferon and p53 -in which these genes are involved and which are common to the examined cell lines were found using PANTHER program. A significant difference in activation of these signaling pathways was discovered in radioresistant and radiosensitive cell lines.Conclusion. Based on the analysis of molecular interaction networks and signaling pathway activation it has been revealed that the greatest differences between radioresistant and radiosensitive cell lines are observed in the activity of Interferon and p53 signaling pathways. TP53 gene expression level is not associated with the activity of p53 signaling pathway. Comparison of gene expression changes and activation of signaling pathways allows us to suggest the expression of DAAM1, IFNAR2, PALLD genes as indicators of radioresistance under radiation exposure.