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The Runx genes: lineage-specific oncogenes and tumor suppressors

Oncogene volume 23, pages 4308–4314 (2004)Cite this article

Abstract

The Runx genes present a challenge to the simple binary classification of cancer genes as oncogenes or tumor suppressors. There is evidence that loss of function of two of the three mammalian Runx genes promotes cancer, but in a highly lineage-restricted manner. In human leukemias, the RUNX1 gene is involved in various chromosomal translocation events that create oncogenic fusion proteins, at least some of which appear to function as dominant-negative inhibitors of the normal gene product. Paradoxically, evidence is mounting that structurally intact Runx genes are also oncogenic when overexpressed. All the three murine genes act as targets for transcriptional activation by retroviral insertional mutagenesis, and the oncogenic potential of Runx2 has been confirmed in transgenic mice. Moreover, the RUNX1 gene is often amplified or overexpressed in cases of acute leukemia. The state of progress in elucidating the oncogenic roles of the Runx genes is the subject of this review, and we draw together recent observations in a tentative model for the effects of Runx deregulation on hematopoietic cell differentiation. We suggest that lineage-specific factors determine the sensitivity to the oncogenic effects of loss or overexpression of Runx factors.

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References

  • Adya N, Stacy T, Speck NA and Liu PP . (1998). Mol. Cell. Biol., 18, 7432–7443.

  • Alvarez Y, Coll MD, Bastida P, Ortega JJ and Caballin MR . (2003). Cancer. Genet. Cytogenet., 140, 58–61.

  • Bangsow C, Rubins N, Glusman G, Bernstein Y, Negreanu V, Goldenberg D, Lotem J, Ben Asher E, Lancet D, Levanon D and Groner Y . (2001). Gene, 279, 221–232.

  • Bernardin F and Friedman AD . (2002). Oncogene, 21, 3247–3252.

  • Bishop JM . (1987). Science, 235, 305–311.

  • Blyth K, Terry A, Mackay N, Vaillant F, Bell M, Cameron ER, Neil JC and Stewart M . (2001). Oncogene, 20, 295–302.

  • Busson-Le Coniat M, Khac FN, Daniel MT, Bernard OA and Berger R . (2001). Genes Chromosomes Cancer, 32, 244–249.

  • Cameron ER, Blyth K, Hanlon L, Kilbey A, Mackay N, Stewart M, Terry A, Vaillant F, Wotton S and Neil JC . (2003). Blood Cells Mol. Dis., 30, 194–200.

  • Canon J and Banerjee U . (2000). Semin. Cell Dev. Biol., 11, 327–336.

  • Cao W, Britos-Bray M, Claxton DF, Kelley CA, Speck NA, Liu PP and Friedman AD . (1997). Oncogene, 15, 1315–1327.

  • Castilla LH, Garrett L, Adya N, Orlic D, Dutra A, Anderson S, Owens J, Eckhaus M, Bodine D and Liu PP . (1999). Nat. Genet., 23, 144–146.

  • Castilla LH, Wijmenga C, Wang Q, Stacy T, Speck NA, Eckhaus M, Marin-Padilla M, Collins FS, Wynshaw-Boris A and Liu PP . (1996). Cell, 87, 687–696.

  • Coffman JA . (2003). Cell Biol. Int., 27, 315–324.

  • Dal Cin P, Atkins L, Ford C, Ariyanayagam S, Armstrong SA, George R, Cleary A and Morton CC . (2001). Genes Chromosomes Cancer, 30, 407–409.

  • de Guzman CG, Warren AJ, Zhang Z, Gartland L, Erickson P, Drabkin H, Hiebert SW and Klug CA . (2002). Mol. Cell. Biol., 22, 5506–5517.

  • Downing JR, Higuchi M, Lenny N and Yeoh AE . (2000). Semin. Cell Dev. Biol., 11, 347–360.

  • Durst KL, Lutterbach B, Kummalue T, Friedman AD and Hiebert SW . (2003). Mol. Cell. Biol., 23, 607–619.

  • Elagib KE, Racke FK, Mogass M, Khetawat R, Delehanty LL and Goldfarb AN . (2003). Blood, 101, 4333–4341.

  • Erickson P, Gao J, Chang KS, Look T, Whisenant E, Raimondi S, Lasher R, Trujillo J, Rowley J and Drabkin H . (1992). Blood, 80, 1825–1831.

  • Fears S, Gavin M, Zhang DE, Hetherington C, Ben David Y, Rowley JD and Nucifora G . (1997). Proc. Natl. Acad. Sci. USA, 94, 1949–1954.

  • Frank R, Zhang J, Uchida H, Meyers S, Hiebert SW and Nimer SD . (1995). Oncogene, 11, 2667–2674.

  • Frank RC, Sun X, Berguido FJ, Jakubowiak A and Nimer SD . (1999). Oncogene, 18, 1701–1710.

  • Golub TR, Barker GF, Bohlander SK, Hiebert SW, Ward DC, Bray-Ward P, Morgan E, Raimondi SC, Rowley JD and Gilliland DG . (1995). Proc. Natl. Acad. Sci. USA, 92, 4917–4921.

  • Harewood L, Robinson H, Harris R, Al Obaidi MJ, Jalali GR, Martineau M, Moorman AV, Sumption N, Richards S, Mitchell C and Harrison CJ . (2003). Leukemia, 17, 547–553.

  • Hasle H . (2001). Lancet Oncol., 2, 429–436.

  • Hayashi K, Abe N, Watanabe T, Obinata M, Ito M, Sato T, Habu S and Satake M . (2001). J. Immunol., 167, 4957–4965.

  • Hiebert SW, Sun W, Davis JN, Golub T, Shurtleff S, Buijs A, Downing JR, Grosveld G, Roussell MF, Gilliland DG, Lenny N and Meyers S . (1996). Mol. Cell. Biol., 16, 1349–1355.

  • Hilgenfeld E, Padilla-Nash H, McNeil N, Knutsen T, Montagna C, Tchinda J, Horst J, Ludwig WD, Serve H, Buchner T, Berdel WE, Schrock E and Ried T . (2001). Br. J. Haematol., 113, 305–317.

  • Jabber Al-Obaidi MS, Martineau M, Bennett CF, Franklin IM, Goldstone AH, Harewood L, Jalali GR, Prentice HG, Richards SM, Roberts K and Harrison CJ . (2002). Leukemia, 16, 669–674.

  • Kakazu N, Taniwaki M, Horiike S, Nishida K, Tatekawa T, Nagai M, Takahashi T, Akaogi T, Inazawa J, Ohki M and Abe T . (1999). Genes Chromosomes Cancer, 26, 336–345.

  • Kanno Y, Kanno T, Sakakura C, Bae SC and Ito Y . (1998). Mol. Cell. Biol., 18, 4252–4261.

  • Kim R, Trubetskoy A, Suzuki T, Jenkins NA, Copeland NG and Lenz J . (2003). J. Virol., 77, 2056–2062.

  • Klampfer L, Zhang J, Zelenetz AO, Uchida H and Nimer SD . (1996). Proc. Natl. Acad. Sci. USA, 93, 14059–14064.

  • Knudson Jr AG . (1986). Annu. Rev. Genet., 20, 231–251.

  • Kogan SC, Lagasse E, Atwater S, Bae SC, Weissman I, Ito Y and Bishop JM . (1998). Proc. Natl. Acad. Sci. USA, 95, 11863–11868.

  • Kurokawa M, Tanaka T, Tanaka K, Hirano N, Ogawa S, Mitani K, Yazaki Y and Hirai H . (1996a). J. Biol. Chem., 271, 16870–16876.

  • Kurokawa M, Tanaka T, Tanaka K, Ogawa S, Mitani K, Yazaki Y and Hirai H . (1996b). Oncogene, 12, 883–892.

  • Lange B . (2000). Br. J. Haematol., 110, 512–524.

  • Lanza C, Volpe G, Basso G, Gottardi E, Perfetto F, Cilli V, Spinelli M, Ricotti E, Guerrasio A, Madon E and Saglio G . (1997). Leukemia, 11, 820–821.

  • Levanon D, Bernstein Y, Negreanu V, Ghozi MC, Bar-Am I, Aloya R, Goldenberg D, Lotem J and Groner Y . (1996). DNA Cell. Biol., 15, 175–185.

  • Levanon D, Bettoun D, Harris-Cerruti C, Woolf E, Negreanu V, Eilam R, Bernstein Y, Goldenberg D, Xiao C, Fliegauf M, Kremer E, Otto F, Brenner O, Lev-Tov A and Groner Y . (2002). EMBO J., 21, 3454–3463.

  • Li J, Shen H, Himmel KL, Dupuy AJ, Largaespada DA, Nakamura T, Shaughnessy Jr JD, Jenkins NA and Copeland NG . (1999). Nat. Genet., 23, 348–353.

  • Li QL, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi XZ, Lee KY, Nomura S, Lee CW, Han SB, Kim HM, Kim WJ, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae SC and Ito Y . (2002). Cell, 109, 113–124.

  • Linggi B, Muller-Tidow C, van de LL, Hu M, Nip J, Serve H, Berdel WE, van der RB, Quelle DE, Rowley JD, Cleveland J, Jansen JH, Pandolfi PP and Hiebert SW . (2002). Nat. Med., 8, 743–750.

  • Liu P, Tarle SA, Hajra A, Claxton DF, Marlton P, Freedman M, Siciliano MJ and Collins FS . (1993). Science, 261, 1041–1044.

  • Lou J, Cao W, Bernardin F, Ayyanathan K, RauscherIII FJ and Friedman AD . (2000). Oncogene, 19, 2695–2703.

  • Lukasik SM, Zhang L, Corpora T, Tomanicek S, Li Y, Kundu M, Hartman K, Liu PP, Laue TM, Biltonen RL, Speck NA and Bushweller JH . (2002). Nat. Struct. Biol., 9, 674–679.

  • Lund AH, Turner G, Trubetskoy A, Verhoeven E, Wientjens E, Hulsman D, Russell R, DePinho RA, Lenz J and van Lohuizen M . (2002). Nat. Genet., 32, 160–165.

  • Lutterbach B, Hou Y, Durst KL and Hiebert SW . (1999). Proc. Natl. Acad. Sci. USA, 96, 12822–12827.

  • Mathew S, Rao PH, Dalton J, Downing JR and Raimondi SC . (2001). Leukemia, 15, 468–472.

  • Meyers S, Lenny N and Hiebert SW . (1995). Mol. Cell. Biol., 15, 1974–1982.

  • Mikhail FM, Serry KA, Hatem N, Mourad ZI, Farawela HM, El Kaffash DM, Coignet L and Nucifora G . (2002). Leukemia, 16, 658–668.

  • Mikkers H, Allen J, Knipscheer P, Romeyn L, Hart A, Vink E and Berns A . (2002). Nat. Genet., 32, 153–159.

  • Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N and Ohki M . (1993). EMBO J., 12, 2715–2721.

  • Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y and Ohki M . (1991). Proc. Natl. Acad. Sci. USA, 88, 10431–10434.

  • Morel F, Herry A, Le Bris MJ, Douet-Guilbert N, Le Calvez G, Marion V, Berthou C and De Braekeeler M . (2002). Cancer Genet. Cytogenet., 137, 142–145.

  • Niini T, Kanerva J, Vettenranta K, Saarinen-Pihkala UM and Knuutila S . (2000). Haematologica, 85, 362–366.

  • Nisson PE, Watkins PC and Sacchi N . (1992). Cancer Genet. Cytogenet., 63, 81–88.

  • Okuda T, Cai Z, Yang S, Lenny N, Lyu CJ, van Deursen JM, Harada H and Downing JR . (1998). Blood, 91, 3134–3143.

  • Okuda T, van Deursen J, Hiebert SW, Grosveld G and Downing JR . (1996). Cell, 84, 321–330.

  • Osato M, Asou N, Abdalla E, Hoshino K, Yamasaki H, Okubo T, Suzushima H, Takatsuki K, Kanno T, Shigesada K and Ito Y . (1999). Blood, 93, 1817–1824.

  • Penther D, Preudhomme C, Talmant P, Roumier C, Godon A, Mechinaud F, Milpied N, Bataille R and Avet-Loiseau H . (2002). Leukemia, 16, 1131–1134.

  • Pozner A, Goldenberg D, Negreanu V, Le SY, Elroy-Stein O, Levanon D and Groner Y . (2000). Mol. Cell. Biol., 20, 2297–2307.

  • Preudhomme C, Warot-Loze D, Roumier C, Grardel-Duflos N, Garand R, Lai JL, Dastugue N, Macintyre E, Denis C, Bauters F, Kerckaert JP, Cosson A and Fenaux P . (2000). Blood, 96, 2862–2869.

  • Robertson A, Dickey C, McCarthy J and Coffman J . (2002). Mech. Dev., 117, 327–330.

  • Romana SP, Mauchauffe M, Le Coniat M, Chumakov I, Le Paslier D, Berger R and Bernard OA . (1995). Blood, 85, 3662–3670.

  • Rowley JD . (1981). Lancet, 2, 1020–1022.

  • Shields PG and Harris CC . (2000). J. Clin. Oncol., 18, 2309–2315.

  • Shimada H, Ichikawa H, Nakamura S, Katsu R, Iwasa M, Kitabayashi I and Ohki M . (2000). Blood, 96, 655–663.

  • Song WJ, Sullivan MG, Legare RD, Hutchings S, Tan X, Kufrin D, Ratajczak J, Resende IC, Haworth C, Hock R, Loh M, Felix C, Roy DC, Busque L, Kurnit D, Willman C, Gewirtz AM, Speck NA, Bushweller JH, Li FP, Gardiner K, Poncz M, Maris JM and Gilliland DG . (1999). Nat. Genet., 23, 166–175.

  • Stewart M, Mackay N, Cameron ER and Neil JC . (2002). J. Virol., 76, 4364–4369.

  • Stewart M, Terry A, Hu M, O’Hara M, Blyth K, Baxter E, Cameron E, Onions DE and Neil JC . (1997). Proc. Natl. Acad. Sci. USA, 94, 8646–8651.

  • Stewart M, Terry A, O’Hara M, Cameron E, Onions D and Neil JC . (1996). J. Gen. Virol., 77, 443–446.

  • Streubel B, Valent P, Lechner K and Fonatsch C . (2001). Cancer Genet. Cytogenet., 124, 42–46.

  • Strom DK, Nip J, Westendorf JJ, Linggi B, Lutterbach B, Downing JR, Lenny N and Hiebert SW . (2000). J. Biol. Chem., 275, 3438–3445.

  • Suzuki T, Shen H, Akagi K, Morse HC, Malley JD, Naiman DQ, Jenkins NA and Copeland NG . (2002). Nat. Genet., 32, 166–174.

  • Tanaka T, Tanaka K, Ogawa S, Kurokawa M, Mitani K, Nishida J, Shibata Y, Yazaki Y and Hirai H . (1995). EMBO J., 14, 341–350.

  • Uchida H, Downing JR, Miyazaki Y, Frank R, Zhang J and Nimer SD . (1999). Oncogene, 18, 1015–1022.

  • Vaillant F, Blyth K, Andrew L, Neil JC and Cameron ER . (2002). J. Immunol., 169, 2866–2874.

  • Vaillant F, Blyth K, Terry A, Bell M, Cameron ER, Neil J and Stewart M . (1999). Oncogene, 18, 7124–7134.

  • Wang Q, Stacy T, Binder M, Marin-Padilla M, Sharpe AH and Speck NA . (1996). Proc. Natl. Acad. Sci. USA, 93, 3444–3449.

  • Wheeler JC, Shigesada K, Gergen JP and Ito Y . (2000). Semin. Cell Dev. Biol., 11, 369–375.

  • Wotton S, Stewart M, Blyth K, Vaillant F, Kilbey A, Neil JC and Cameron ER . (2002). Cancer Res., 62, 7181–7185.

  • Yang Y, Wang W, Cleaves R, Zahurak M, Cheng L, Civin CI and Friedman AD . (2002). Cancer Res., 62, 2232–2235.

  • Yergeau DA, Hetherington CJ, Wang Q, Zhang P, Sharpe AH, Binder M, Marin-Padilla M, Tenen DG, Speck NA and Zhang DE . (1997). Nat. Genet., 15, 303–306.

  • Zaiman AL, Lewis AF, Crute BE, Speck NA and Lenz J . (1995). J. Virol., 69, 2898–2906.

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Acknowledgements

We thank Monica Stewart and Karen Blyth for critical reading of the manuscript. The Molecular Oncology group is supported by the Leukaemia Research Fund of Great Britain, Cancer Research UK and the Association for International Cancer Research.

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  1. Molecular Oncology Laboratory, Institute of Comparative Medicine, University of Glasgow Veterinary School, Glasgow, G61 1QH, UK

    Ewan R Cameron & James C Neil

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Cameron, E., Neil, J. The Runx genes: lineage-specific oncogenes and tumor suppressors. Oncogene 23, 4308–4314 (2004). https://doi.org/10.1038/sj.onc.1207130

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