Identification of p53-regulated Genes in Human Cancer Cells by Genome-wide Transcription Profiling with cDNA Microarray

Abstract

p53 is a well-studied tumor suppressor gene. Many conventional methods have been employed to identify p53 function-associated genes. In order to identify p53 regulated genes, cDNA microarray was used to study the genome-wide transcriptional expression pattern of the human large-cell lung cancer cell line H1299 transfected with a temperature sensitive mutant p53 construct, p53(superscript V173L). To identify the downstream genes to p53, the cell line H1299-p53(superscript V173L) was used for the experiments since the cells express protein with assumed wild-type p53 protein function upon temperature shift from 37℃ to 32℃. After temperature shift from 37℃ to 32℃, cells were harvested at the following time intervals: 0, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours. By the microarray analysis, a total of 89 genes were identified as p53 up-regulated or p53 down-regulated genes. The majority of these genes are related to signal transduction, cell cycle regulation, metabolism regulation, and DNA repair. Among these genes, the MHC (major compatibility complex) class I genes, which play major roles in immune responses were significantly and consistently induced by p53. This indicates that p53 may involve in certain immune response pathways to target stressed cells or tumor cells for elimination.