Abstract 441: Identification of genes with differential expression in induced radio-resistant human colorectal cancer cell lines. (2013)

Abstract Colorectal cancer (CRC) is the third most common type of cancer in developed countries. Proper radiotherapy with chemotherapy is the worldwide treatment for CRC patients. It has been reported that chemoradiotherapy is related to chemical and radiation resistance and may cause local recurrence. To investigate features in resistant tumors, various cancer cell lines that have resistance to chemo and radiotherapy have been established. In this study, three radio-resistant human colorectal cancer cell lines (SNU-61R80GY, SNU-283R80GY, and SNU-503R80GY) were induced by exposing them to a total of 80 greys of Cs-137 to define their characteristics compared to their parental cell lines (SNU-61, SNU-283, and SNU-503). In order to explain cellular properties of parental and induced radio-resistant cell lines, cell proliferation assay, soft agar colony forming assay, cell cycle analysis, and apoptotic assay were performed. Interestingly, remarkable increases of cell proliferation and colony forming abilities on the induced radio-resistant cell line (SNU-503R80GY) were observed compared to the parental cell line (SNU-503) without irradiation although there was no significant change with cell cycle and apoptotic assay using FACS and western blot analysis. Gene expression microarray analysis was then conducted to identify genetic differences between the induced radio-resistant cell lines and the parental cell lines and thirty-three genes with more than 2-fold up-regulated upon induced radio-resistant cell lines were analyzed. According to the gene ontology analysis of these genes, most of them were associated with responses to hypoxia and oxygen levels, oxidation reduction, regulation of epithelial cell differentiation, and cell-cell adhesion. Five genes with more than 3-fold up-regulated upon all three induced radio-resistant cell lines were also sorted out as candidate marker genes for radio-resistance. Furthermore, various genes that are related with cell migration, growth, differentiation, adhesion, and ERBB signaling pathways were screened by RT-PCR. In conclusion, induced radio-resistant human colorectal cancer cell lines have different features such as differential gene expression patterns, and a great ability of cell proliferation, and colony forming compared to the parental cell lines. These results suggest that the induced radio-resistant cell lines are more tumorigenic than the parental cell lines. These cellular and genetic characteristics on the induced radio-resistant cell lines could be considered markers for radio-resistance. The genes that were 3-fold up-regulated on the induced radio-resistant cell lines could be also regarded as candidate markers for radio-resistance. In order to verify our hypothesis, we are in the process of performing the same experiments using other human colorectal cancer cell lines. Citation Format: Ye-Ah Kim, Sang-Geun Jang, Young-Kyoung Shin, Ja-Lok Ku. Identification of genes with differential expression in induced radio-resistant human colorectal cancer cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 441. doi:10.1158/1538-7445.AM2013-441