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

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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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References

  • Bakin AV and Curran T . (1999). Science, 283, 387–390.

  • Buttner C, Skupin A and Rieber EP . (2004). J Cell Physiol, 198, 248–258.

  • Eferl R and Wagner E . (2003). Nat Rev Cancer, 3, 859–868.

  • Garcia E, Marcos-Gutierrez C, del Mar Lorente M, Moreno JC and Vidal M . (1999). EMBO J, 18, 3404–3418.

  • Gottlicher M, Minucci S, Zhu P, Kramer OH, Schimpf A, Giavara S, Sleeman JP, Lo Coco F, Nervi C, Pelicci PG and Heinzel T . (2001). EMBO J, 20, 6969–6978.

  • Grunstein M . (1997). Nature, 389, 349–352.

  • Hennigan RF, Hawker KL and Ozanne BW . (1994). Oncogene, 9, 3591–3600.

  • Imai T, Adachi S, Nishijo K, Ohgushi M, Okada M, Yasumi T, Watanabe K, Nishikomori R, Nakayama T, Yonehara S, Toguchida J and Nakahata T . (2003). Oncogene, 22, 9231–9242.

  • Johnston IM, Spence HJ, Winnie JN, McGarry L, Vass JK, Meagher L, Stapleton G and Ozanne BW . (2000). Oncogene, 19, 5348–5358.

  • Kelly WK, O'Connor OA and Marks PA . (2002). Expert Opin Invest Drugs, 11, 1695–1713.

  • Kouzarides T . (2000). EMBO J, 19, 1176–1179.

  • Kuo MH and Allis CD . (1998). Bioessays, 20, 615–626.

  • Kwon HJ, Owa T, Hassig CA, Shimada J and Schreiber SL . (1998). Proc Natl Acad Sci USA, 95, 3356–3361.

  • Lamb RF, Hennigan RF, Turnbull K, Katsanakis KD, MacKenzie ED, Birnie GD and Ozanne BW . (1997a). Mol Cell Biol, 17, 963–976.

  • Lamb RF, Ozanne BW, Roy C, McGarry L, Stipp C, Mangeat P and Jay DG . (1997b). Curr Biol, 7, 682–688.

  • Lehrmann H, Pritchard LL and Harel-Bellan A . (2002). Adv Cancer Res, 86, 41–65.

  • Liu LT, Chang HC, Chiang LC and Hung WC . (2003). Cancer Res, 63, 3069–3072.

  • Marks PA, Miller T and Richon VM . (2003). Curr Opin Pharmacol, 3, 344–351.

  • Masui T, Doi R, Koshiba T, Fujimoto K, Tsuji S, Nakajima S, Koizumi M, Toyoda E, Tulachan S, Ito D, Kami K, Mori T, Wada M, Noda M and Imamura M . (2003). Clin Cancer Res, 9, 1779–1784.

  • Matsumoto M, Matsutani S, Sugita K, Yoshida H, Hayashi F, Terui Y, Nakai H, Uotani N, Kawamura Y, Matsumoto K, Shoji J and Yoshida T . (1992). J Antibiotics (Tokyo), 45, 879–885.

  • McGaha TL, Le M, Kodera T, Stoica C, Zhu J, Paul WE and Bona CA . (2003). Arthritis Rheum, 48, 2275–2284.

  • Ozanne BW, McGarry L, Spence HJ, Johnston I, Winnie J, Meagher L and Stapleton G . (2000). Eur J Cancer, 36, 1640–1648.

  • Quelle FW, Shimoda K, Thierfelder W, Fischer C, Kim A, Ruben SM, Cleveland JL, Pierce JH, Keegan AD, Nelms K, Paul WE and Ihle JN . (1995). Mol Cell Biol, 15, 3336–3343.

  • Rosato RR, Almenara JA and Grant S . (2003). Cancer Res, 63, 3637–3645.

  • Sambrook J, Fritsch EF and Maniatis T . (1989). Molecular Cloning. A Laboratory Manual, 2 edn Cold Spring Harbour Laboratory Press: Cold Spring Harbor, NY.

    Google Scholar 

  • Sano K, Tanihara H, Heimark RL, Obata S, Davidson M, St John T, Taketani S and Suzuki S . (1993). EMBO J, 12, 2249–2256.

  • Schlisio S, Halperin T, Vidal M and Nevins JR . (2002). EMBO J, 21, 5775–5786.

  • Scott LA, Vass JK, Parkinson EK, Gillespie DAF, Winnie JN and Ozanne BW . (2004). Mol Cell Biol, 24, 1540–1559.

  • Spence HJ, Johnston I, Ewart K, Buchanan SJ, Fitzgerald U and Ozanne BW . (2000). Oncogene, 19, 1266–1276.

  • Stapleton G, Malliri A and Ozanne BW . (2002). J Cell Sci, 115, 2713–2724.

  • Sugita K, Yoshida H, Matsumoto M and Matsutani S . (1992). Biochem Biophys Res Commun, 182, 379–387.

  • Suzuki ST . (2000). Exp Cell Res, 261, 13–18.

  • Timmermann S, Lehrmann H, Polesskaya A and Harel-Bellan A . (2001). Cell Mol Life Sci, 58, 728–736.

  • Trimarchi JM, Fairchild B, Wen J and Lees JA . (2001). Proc Natl Acad Sci USA, 98, 1519–1524.

  • Yamashita Y, Shimada M, Harimoto N, Rikimaru T, Shirabe K, Tanaka S and Sugimachi K . (2003). Int J Cancer, 103, 572–576.

  • Yoshida M, Kijima M, Akita M and Beppu T . (1990). J Biol Chem, 265, 17174–17179.

  • Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P and Reinberg D . (1997). Cell, 89, 357–364.

  • Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A and Reinberg D . (1999). Genes Dev, 13, 1924–1935.

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

    Lynn C McGarry, Joseph N Winnie & Bradford W Ozanne

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  1. Lynn C McGarry
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  2. Joseph N Winnie
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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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