Identification of Genes with Differential Expression in Induced Radio-resistant Human Colorectal Cancer Cell Lines

Abstract

To investigate features in resistant colorectal cancer cells, three radio-resistant human colorectal cancer cell lines (SNU-61R80GY, SNU-283R80GY, and SNU-503R80GY) were induced from their parental cell lines (SNU-61, SNU-283, and SNU-503) by exposing them to a total of 80 grays of Cesium-137. Interestingly, remarkable increases in cell proliferation and colony forming abilities for SNU-503R80GY were observed compared to SNU-503 without irradiation although there were no significant changes in the cell cycle and apoptotic assays using FACS and western blot analysis. Gene expression microarray analysis was then conducted to identify genetic differences between the induced radio-resistant colorectal cancer cell lines and the parental cell lines. Thirty-three genes that were more than 2-fold up or down-regulated in the induced radio-resistant colorectal cancer cell lines were analyzed. Five genes that were 3-fold up-regulated in all three induced radio-resistant colorectal cancer cell lines were sorted out as candidate marker genes for radio-resistance and ERBB receptor feedback inhibitor 1 (ERRFI1, also known as MIG6, GENE33 or RALT) was selected for siRNA transfection and functional study. I discovered that the induced radio-resistant human colorectal cancer cell lines have different features such as different gene expression patterns, and their ability for cell proliferation and colony forming is greatly enhanced compared to the parental cell lines. These results suggest that the induced radio-resistant colorectal cancer cell lines are more tumorigenic than the parental cell lines. These cellular and genetic characteristics of the induced radio-resistant colorectal cancer cell lines could be considered as markers for radio-resistance. The genes that were 3-fold up-regulated in the induced radio-resistant colorectal cancer cell lines could be also regarded as candidate markers for radio-resistance.