Oligonucleotide microarrays for studying the effects of Ras signal transduction on the genetic program

Abstract

Cytoplasmic signal transduction processes are tightly coupled with the transcriptional regulation of genes executing cellular phenotypes in normal conditions and in disease. A major challenge in signal transduction research is to understand how the specificity of the transcriptional response is determined by complex networks of signaling effectors and transcription factors. The Ras signal transduction pathway belongs to the few characterized pathways triggering malignant phenotypes both in experimental and human cancer. We have developed an array-based tool which permits analysis of Ras signaling on transcription under various experimental conditions as well as in tumor specimens. The composition of targets represented on the Ras signaling target array (RASTA) is based on previously validated gene expression profiles and published functional studies. The Ras signaling target array was used to compare the transcriptional response toward oncogenic Ras in fibroblasts and epithelial cells and to assess the time-dependent deregulation of target genes.