Gene transcription in a set of 49 human primary lungadenocarcinomas and 9 normal lung tissue sampleswas examined using Affymetrix GeneChip technology.A total of 3442 genes, called the set MAD,were found to be either up- or down-regulated byat least 2-fold between the two phenotypes. Genesassigned to a particular gene ontology term werefound, in many cases, to be significantly unevenlydistributed between the genes in and outside MAD.Terms that were overrepresented in MAD includedfunctions directly implicated in the cancer cellmetabolism. Based on their functional roles andexpression profiles, genes in MAD were groupedinto likely co-regulated gene sets. Highly conservedsequences in the 5 kb region upstream of the genesin these sets were identified with the motif discoverytool, MoDEL. Potential oncogenic transcription factorsand their corresponding binding sites wereidentified in these conserved regions using theTRANSFAC 8.3 database. Several of the transcriptionfactors identified in this study have beenshown elsewhere to be involved in oncogenic processes.This study searched beyond phenotypicgene expression profiles in cancer cells, in orderto identify the more important regulatory transcriptionfactors that caused these aberrations in geneexpression.