Solute carrier protein family may involve in radiation-induced radioresistance of non-small cell lung cancer

Purpose To find new signaling pathways that may be involved in the cellular response to ionizing radiation. Methods Two radioresistant subclones (A549/R and SPCA1/R) derived from lung adenocarcinoma cell lines A549 and SPCA1 were established after eight rounds of sublethal irradiation. The new subclones were tested for radioresistant features using clonogenic assay and apoptosis analysis. The genes expressed differentially were screened with cDNA microarray analysis consisting of 48,000 transcript probes and confirmed by quantitative real-time PCR. Results Stable and significant radioresistance was observed in the screened subclones. The microarray analysis showed 65 genes were up-regulated and 141 genes down-regulated in SPCA1/R cells. The up-regulated and down-regulated genes were 708 and 230 in A549/R cells, respectively. Twenty-seven altered genes were consistent in both subclones. Interestingly, members the of human solute carrier (SLC) gene superfamily were among in 27 genes. Conclusions The differentially expressed genes in both cell lines may contribute to their radioresistant phenotype. This extensive list of genes identified in the experiment provides a large body of potentially valuable information for studying the molecular mechanism(s) of radiosensitivity and identification of candidate molecular markers of radiation sensitivity. Thus, to our knowledge, the SLC gene superfamily is the first being reported to involve in acquired radioresistance.