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  • Original Paper
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Invasion of v-FosFBR-transformed cells is dependent upon histone deacetylase activity and suppression of histone deacetylase regulated genes

Abstract

Transformation of fibroblasts with the v-fos oncogene produces a highly invasive phenotype that is mediated by changes in gene expression. Inhibition of histone deacetylase (HDAC) activity with trichostatin A (TSA) or valproic acid (VPA) at concentrations that do not affect morphology, motility, chemotaxis or proliferation, strongly inhibits invasion and results in the re-expression of a significant proportion of those genes that are downregulated in the v-Fos-transformed cells. Independent expression of three of these re-expressed genes, (Ring1 and YY1 binding protein (RYBP); protocadherin gamma subfamily C,3 (PCDHGC3); and signal transducer and activator of transcription 6 (STAT6)) in Fos-transformed cells, has no effect on morphology, motility, chemotaxis or proliferation, but strongly inhibits invasion. Therefore, we conclude that the ability of v-Fos-transformed cells to invade is dependent upon repression of gene expression through either direct or indirect HDAC activity.

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Acknowledgements

We thank Linda Scott, Heather Spence, Genevieve Stapleton and David Gillespie for helpful discussion; Margaret O'Prey and Peter McHardy for technical help with imaging; and Robert McFarlane and Christine Lang for PCR primer synthesis and DNA sequencing. We also thank Tony Kouzarides, Wellcome/CRUK Institute and Department of Pathology, Cambridge, UK, for helpful discussion; and Miguel Vidal, Centro De Investigaciones Biologicas, Madrid, Spain; James Ihle, St Jude Children's Research Hospital, Memphis, USA; and Shintaro T Suzuki, Kwanseigakuin University, Hyogo, Japan for gifts of cDNAs. This work was funded by Cancer Research UK.

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Correspondence to Bradford W Ozanne.

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McGarry, L., Winnie, J. & Ozanne, B. Invasion of v-FosFBR-transformed cells is dependent upon histone deacetylase activity and suppression of histone deacetylase regulated genes. Oncogene 23, 5284–5292 (2004). https://doi.org/10.1038/sj.onc.1207687

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