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Microarray analysis identifies Autotaxin, a tumour cell motility and angiogenic factor with lysophospholipase D activity, as a specific target of cell transformation by v-Jun

Oncogene volume 23, pages 2357–2366 (2004)Cite this article

Abstract

We have used chicken cDNA microarrays to investigate gene-expression changes induced during transformation of chick embryo fibroblasts (CEF) by the viral Jun oncoprotein encoded by ASV17. This analysis reveals that v-Jun induces increases and decreases of varying magnitude in the expression of genes involved in diverse cellular functions, most of which have not been detected in previous screens for putative v-Jun targets. In all, 27 individual genes were identified, whose expression is increased threefold or more in v-Jun-transformed cells, including genes involved in energy generation, protein synthesis, and gene transcription. Interestingly, this group includes the hypoxia-inducible factor-1 alpha (Hif-1α) transcription factor and the glycolytic enzyme enolase, suggesting that adaptation to hypoxia could play a role in tumorigenesis by v-Jun. We also identified 32 genes whose expression is decreased threefold or more, including chaperones, components of the cytoskeleton, and, unexpectedly, DNA replication factors. The gene whose expression is upregulated most dramatically (∼100-fold) encodes Autotaxin (ATX), a secreted tumor motility-promoting factor with lysophospholipase D activity. Strikingly, v-Jun-transformed CEF secrete catalytically active ATX and chemotactic activity, which can be detected in conditioned medium. ATX is not detectably expressed in normal CEF or CEF transformed by the v-Src or v-Myc oncoproteins, indicating that induction of this putative autocrine/paracrine factor is a specific consequence of cell transformation by v-Jun. ATX has been implicated in both angiogenesis and invasion, and could therefore play an important role in tumorigenesis by v-Jun in vivo.

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Acknowledgements

We are grateful to Dr K Vass and A Kotwaliwale for help with initial computer analysis of the microarray data, and to Professor JA Wyke, Dr K Ryan, and Professor B Ozanne for comments on the manuscript. This work was supported by Cancer Research UK (formerly Cancer Research Campaign of the UK) and also by National Cancer Institute Grant RO1 CA20068 (to PN).

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Authors and Affiliations

  1. Beatson Institute for Cancer Research, Cancer Research Campaign Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK

    Elizabeth J Black & David A F Gillespie

  2. Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, 20892, MD, USA

    Timothy Clair

  3. Divisions of Basic Sciences and Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, 98109-1024, WA, USA

    Jeffrey Delrow & Paul Neiman

  4. Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK

    David A F Gillespie

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  1. Elizabeth J Black
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Correspondence to David A F Gillespie.

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Black, E., Clair, T., Delrow, J. et al. Microarray analysis identifies Autotaxin, a tumour cell motility and angiogenic factor with lysophospholipase D activity, as a specific target of cell transformation by v-Jun. Oncogene 23, 2357–2366 (2004). https://doi.org/10.1038/sj.onc.1207377

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