Research

A transcriptome map of cellular transformation by the fos oncogene

Jared M Ordway^{* 2} , Steven D Fenster^{* 1} , Hong Ruan¹ and Thomas Curran¹

¹Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 332 N. Lauderdale St., Memphis, TN, 38105, USA

²Orion Genomics, 4041 Forest Park Ave., St. Louis, MO, 63108, USA

author email corresponding author email* Contributed equally

Molecular Cancer 2005, 4:19doi:10.1186/1476-4598-4-19

Published:	26 May 2005

Abstract

Background

The c-fos gene was originally identified as the cellular homolog of the oncogene v-fos carried by the Finkel-Biskis-Jenkins and Finkel-Biskis-Reilly murine osteogenic sarcoma retroviruses. Sustained expression of fos is sufficient to induce cellular transformation in vitro and tumorigenesis in vivo. 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 fos. We have extended these studies by constructing a cellular system for conditional transformation by v-fos. Using Affymetrix-based DNA microarray technology, we analyzed transcriptional changes over the course of transformation and reversion in an inducible v-fos system.

Results

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.

Conclusion

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.