Microarray Approaches for Analysis of Tumor Suppressor Gene Function

Many tumor suppressor genes are known to function at least in part through regulation of the transcription of downstream effector genes (Table 1 ). A major example of such a transcriptional regulator is p53, one of the most commonly mutated tumor suppressor genes in human cancer (1 ) and hence one of the most exhaustively studied. Estimates based on a survey of p53 binding sites in the genome put the number of p53-regulated genes at several hundred (2 ), while the finding that p53 can affect the expression of some genes in the absence of direct DNA binding may increase this number (3 ). Genes known to be regulated by p53 play roles in many important cellular processes, including cell cycle progression, DNA repair, and apoptosis (Table 2 ). Loss of such a tumor suppressor gene can disrupt the regulation of multiple genes, affecting numerous cellular pathways and leading to a variety of phenotypic changes. Comparative analysis of complex patterns of gene expression can therefore provide a powerful tool to develop insight into mechanisms of tumor suppressor gene function involving transcriptional regulation. Table 1  Tumor Suppressor Genes That Can Act as Transcription Factors

Table 2  Examples of Tp53 Effector Genes with Roles in Cellular Stress Processes