A transcriptome map of cellular transformation by the fos oncogene

Microarray analyses of temporal gene expression during the process of v-fos mediated cellular transformation and morphological reversion revealed a remarkably dynamic transcriptome. Of the more than 8000 genes analyzed in this study, 3766 genes were categorized into 18 gene-expression patterns by using self-organizing map analysis. By combining the analysis of gene expression profiles in stably transformed cells with the analysis of sequential expression patterns during conditional transformation, we identified a relatively small cohort of genes implicated in v-fos mediated cellular transformation.This approach defines a general conditional cell transformation system that can be used to study the endogenous transcription regulatory mechanisms involved in transformation and tumorigenesis. In addition, this study is the first reported analysis of dynamic changes in gene expression throughout experimentally controlled morphological transformation mediated by v-fos.The c-fos proto-oncogene encodes an immediate-early transcription factor that is rapidly and transiently induced by a variety of extracellular stimuli associated with cellular responses such as proliferation, differentiation, apoptosis and neuronal signalling [1]. The c-Fos protein functions by forming leucine zipper dimers with members of the Jun and ATF/CREB families that comprise the transcription factor complexes collectively referred to as AP-1 [2]. The tightly regulated expression and activity of AP-1 family members defines a prototypical mechanism whereby short-term extracellular signals are coupled to appropriate long-term changes in cellular phenotype by selective regulation of gene expression.The identification of v-fos as the oncogene carried by the Finkel-Biskis-Jenkins and Finkel-Biskis-Reilly murine osteosarcoma retroviruses contributed to the realization that tumorigenic retroviruses harbor viral versions of cellular genes and that these genes can elude the regulatory constraints imposed upon t