Summary: | <p>Abstract</p> <p>Background</p> <p>The c-<it>fos </it>gene was originally identified as the cellular homolog of the oncogene v-<it>fos </it>carried by the Finkel-Biskis-Jenkins and Finkel-Biskis-Reilly murine osteogenic sarcoma retroviruses. Sustained expression of <it>fos </it>is sufficient to induce cellular transformation <it>in vitro </it>and tumorigenesis <it>in vivo</it>. Fos functions as a component of the AP-1 transcription factor complex to regulate gene transcription and several differentially expressed genes have been identified in cells transformed by <it>fos</it>. We have extended these studies by constructing a cellular system for conditional transformation by v-<it>fos</it>. Using Affymetrix-based DNA microarray technology, we analyzed transcriptional changes over the course of transformation and reversion in an inducible v-fos system.</p> <p>Results</p> <p>Microarray analyses of temporal gene expression during the process of <it>v-fos </it>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 <it>v-fos </it>mediated cellular transformation.</p> <p>Conclusion</p> <p>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-<it>fos</it>.</p>
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