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Transcription repression in oncogenic transformation: common targets of epigenetic repression in cells transformed by Fos, Ras or Dnmt1

Oncogene volume 23, pages 3737–3748 (2004)Cite this article

Abstract

Fos and Ras function in both dependent and independent signal transduction pathways, and sustained activity of either oncogene is sufficient to induce cell transformation and tumorigenesis. Increased DNA (cytosine-5) methyltransferse (Dnmt1) activity is involved in the mechanism of transformation by both oncogenes, suggesting that inappropriate epigenetic transcription regulation may be a common route of oncogenesis, and that cell transformation may model aspects of the epigenetic deregulation that often occurs in tumors. Here, we have taken a microarray-based gene expression approach to identify differentially expressed genes in cells transformed by c-fos, v-fos, ras or Dnmt1. The cohort of genes differentially expressed in all four transformation systems includes an over-representation of repressed genes, many of which have been functionally implicated in the suppression of transformation or tumorigenesis. Furthermore, we identified four potential tumor suppressor genes subject to epigenetic transcriptional repression in transformed cells. The results emphasize the role of transcription repression in oncogenesis, and they provide insights into the potential common epigenetic mechanisms impacting cell transformation.

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Acknowledgements

We thank John J Morris, Dr Dyvian Patel and the St Jude Childrens Research Hospital Clinical Applications Core Technology Center for generation of microarray data and advice related to data analysis, Dr Edwin Liu and Mei He for training, Wanyun Zhong and Jack Sublett for technical assistance, Hong Ruan, Jennifer L Campbell and the Hartwell Center for Bioinformatics and Biotechnology for website development, and Drs Hiromichi Kimura and Susan Magdaleno for critical review of the manuscript. This work was supported by the National Institutes of Health grant RO1 CA 84139 (TC), training in the Biology of Cancer grant CA 09346-20 (JMO) and the American Lebanese Syrian Associated Charities (ALSAC).

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

    Jared M Ordway & Tom Curran

  2. Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK

    Katy Williams

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Correspondence to Tom Curran.

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Ordway, J., Williams, K. & Curran, T. Transcription repression in oncogenic transformation: common targets of epigenetic repression in cells transformed by Fos, Ras or Dnmt1. Oncogene 23, 3737–3748 (2004). https://doi.org/10.1038/sj.onc.1207483

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