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  • Original Paper
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Tel induces a G1 arrest and suppresses Ras-induced transformation

Oncogene volume 19, pages 5244–5250 (2000)Cite this article

Abstract

The Tel gene is a major target of translocations in leukemia and loss of heterozygosity is regularly observed for the non-translocated allele, thus supporting the notion that Tel is a tumor suppressor. Most tumor suppressors influence cellular proliferation, differentiation and cell death and thereby prevent oncogenic transformation and genetic instability. We found that overexpression of Tel retards proliferation of many cell types, primary cells and immortalized cells, by inducing a G1 arrest. Tel's block of cellular proliferation is rescued by high seeding densities. Furthermore, Tel suppressed Ras-mediated colony growth in soft agar and tumor formation in nude mice. The Pointed and DNA binding (DB) domains of Tel were required for all Tel-induced phenotypes.

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References

  • Baens M, Wlodarska I, Corveleyn A, Hoornaert I, Hagemeijer A and Marynen P. . 1999 Genomics 56: 40–50.

  • Buijs A, Sherr S, van Baal S, van Bezouw S, van der Plas D, Geurts van Kessel A, Riegman P, Lekanne Deprez R, Zwarthoff E, Hagemeijer A and Grosveld G. . 1995 Oncogene 10: 1511–1519.

  • Carroll M, Tomasson MH, Barker GF, Golub TR and Gilliland DG. . 1996 Proc. Natl. Acad. Sci. USA 93: 14845–14850.

  • Cazzaniga G, Tosi S, Aloisi A, Giudici G, Daniotti M, Pioltelli P, Kearney L and Biondi A. . 1999 Blood 94: 4370–4373.

  • Chakrabarti SR and Nucifora G. . 1999 Biochem. Biophys. Res. Commun. 264: 871–877.

  • Chakrabarti SR, Sood R, Ganguly S, Bohlander S, Shen Z and Nucifora G. . 1999 Proc. Natl. Acad. Sci. USA 96: 7467–7472.

  • Chase A, Reiter A, Burci L, Cazzaniga G, Biondi A, Pickard J, Roberts IA, Goldman JM and Cross NC. . 1999 Blood 93: 1025–1031.

  • Cools J, Bihou-Nabera C, Wlodarska I, Cabrol C, Talmant P, Bernard P, Hagemeijer A and Marynen P. . 1999 Blood 94: 1820–1824.

  • Du W, Lebowitz PF and Prendergast GC. . 1999 Cancer Res. 59: 2059–2063.

  • Eguchi M, Eguchi-Ishimae M, Tojo A, Morishita K, Suzuki K, Sato Y, Kudoh S, Tanaka K, Setoyama M, Nagamura F, Asano S and Kamada N. . 1999 Blood 93: 1355–1363.

  • Fenrick R, Amann JM, Lutterbach B, Wang L, Westendorf JJ, Downing JR and Hiebert SW. . 1999 Mol. Cell. Biol. 19: 6566–6574.

  • Foos G, Garcia-Ramirez JJ, Galang CK and Hauser CA. . 1998 J. Biol. Chem. 273: 18871–18880.

  • Galang CK, Garcia-Ramirez J, Solski PA, Westwick JK, Der CJ, Neznanov NN, Oshima RG and Hauser CA. . 1996 J. Biol. Chem. 271: 7992–7998.

  • Golub T, McLean T, Stegmaier K, Carroll M, Tomasson M and Gilliland DG. . 1996a Biochim. Biophys. Acta 1288: 7–10.

  • 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.

  • Golub TR, Barker GF, Lovett M and Gilliland DG. . 1994 Cell 77: 307–316.

  • Golub TR, Goga A, Barker GF, Afar DE, McLaughlin J, Bohlander SK, Rowley JD, Witte ON and Gilliland DG. . 1996b Mol. Cell. Biol. 16: 4107–4116.

  • Graves BJ and Petersen JM. . 1998 Adv. Cancer Res. 75: 1–55.

  • Hoglund M, Johansson B, Pedersen-Bjergaard J, Marynen P and Mitelman F. . 1996 Blood 87: 324–330.

  • Iijima Y, Ito T, Oikawa T, Eguchi M, Eguchi-Ishimae M, Kamada N, Kishi K, Asano S, Sakaki Y and Sato Y. . 2000 Blood 95: 2126–2131.

  • Jousset C, Carron C, Boureux A, Quang C, Oury C, Dusanter-Fourt I, Charon M, Levin J, Bernard O and Ghysdael J. . 1997 EMBO J 16: 69–82.

  • Knezevich S, Garnett M, Pysher T, Beckwith J, Grundy P and Sorensen P. . 1998a Cancer Res. 58: 5046–5048.

  • Knezevich S, McFadden D, Tao W, Lim J and Sorensen P. . 1998b Nat. Genet. 18: 184–187.

  • Kwiatkowski B, Zielinska-Kwiatkowska A and Hickstein D. . 1999 American Society of Hematology, Vol. 94. W.B. Saunders Company, A Division of Harcourt Brace and Company: New Orleans, LA pp 1155A.

  • Kwiatkowski BA, Bastian LS, Bauer Jr. TR, Tsai S, Zielinska-Kwiatkowska AG and Hickstein DD. . 1998 J. Biol. Chem. 273: 17525–17530.

  • La Starza R, Stella M, Testoni N, Di Bona E, Ciolli S, Marynen P, Martelli MF, Mandelli F and Mecucci C. . 1999 Br. J. Haematol. 107: 340–346.

  • Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, Berthou C, Lessard M, Berger R, Ghysdael J and Bernard OA. . 1997 Science 278: 1309–1312.

  • Langer SJ, Bortner DM, Roussel MF, Sherr CJ and Ostrowski MC. . 1992 Mol. Cell. Biol. 12: 5355–5362.

  • Liu Q, Schwaller J, Kutok J, Cain D, Aster JC, Williams IR and Gilliland DG. . 2000 EMBO J 19: 1827–1838.

  • Lopez RG, Carron C, Oury C, Gardellin P, Bernard O and Ghysdael J. . 1999 J. Biol. Chem. 274: 30132–30138.

  • May W, Lessnick S, Braun B, Klemsz M, Lewis B, Lunsford L, Hromas R and Denny C. . 1993 Mol. Cell. Biol. 13: 7393–7398.

  • Muller AJ, Young JC, Pendergast A, Pondel M, Landau NR, Littman DR and Witte ON. . 1991 Mol. Cell. Biol. 11: 1785–1792.

  • Papadopoulos P, Ridge SA, Boucher CA, Stocking C and Wiedemann LM. . 1995 Cancer Res. 55: 34–38.

  • Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H and Marynen P. . 1997a Blood 90: 2535–2540.

  • Peeters P, Wlodarska I, Baens M, Criel A, Selleslag D, Hagemeijer A, Van den Berghe H and Marynen P. . 1997b Cancer Res. 57: 564–569.

  • Poirel H, Oury C, Carron C, Duprez E, Laabi Y, Tsapis A, Romana SP, Mauchauffe M, Le Coniat M, Berger R, Ghysdael J and Bernard OA. . 1997 Oncogene 14: 349–357.

  • Potter M, Buijs A, Kreider B, Rompaey LV and Grosveld G. . 2000 Blood 95: 3341–3348.

  • Ritchie KA, Aprikyan AA, Bowen-Pope DF, Norby-Slycord CJ, Conyers S, Bartelmez S, Sitnicka EH and Hickstein DD. . 1999 Leukemia 13: 1790–1803.

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

  • Rowley JD. . 1999 Semin. Hematol. 36: 59–72.

  • Sato Y, Bohlander SK, Kobayashi H, Reshmi S, Suto Y, Davis EM, Espinosa R, Hoopes R, Montgomery KT, Kucherlapati RS, Le Beau MM and Rowley JD. . 1997 Blood 90: 4886–4893.

  • Sato Y, Suto Y, Pietenpol J, Golub TR, Gilliland DG, Davis EM, Le Beau MM, Roberts JM, Vogelstein B, Rowley JD and Bohlander S. . 1995 Blood 86: 1525–1533.

  • Schwaller J, Frantsve J, Aster J, Williams IR, Tomasson MH, Ross TS, Peeters P, Van Rompaey L, Van Etten RA, Ilaria Jr R, Marynen P and Gilliland DG. . 1998 EMBO J 17: 5321–5333.

  • Sgouras DN, Athanasiou MA, Beal Jr GJ, Fisher RJ, Blair DG and Mavrothalassitis GJ. . 1995 EMBO J 14: 4781–4793.

  • Shumaker DK, Sklar MD, Prochownik EV and Varani J. . 1994 Exp. Cell. Res. 214: 440–446.

  • Shurtleff SA, Buijs A, Behm FG, Rubnitz JE, Raimondi SC, Hancock ML, Chan GC, Pui CH, Grosveld G and Downing JR. . 1995 Leukemia 9: 1985–1989.

  • Stegmaier K, Pendse S, Barker GF, Bray-Ward P, Ward DC, Montgomery KT, Krauter KS, Reynolds C, Sklar J, Donnelly M, Bohlander S, Rowley J, Sallan S, Gilliland DG and Golub TR. . 1995 Blood 86: 38–44.

  • Stegmaier K, Takeuchi S, Golub TR, Bohlander SK, Bartram CR and Koeffler HP. . 1996 Cancer Res. 56: 1413–1417.

  • Suto Y, Sato Y, Smith SD, Rowley JD and Bohlander SK. . 1997 Genes Chromosomes Cancer 18: 254–268.

  • Takeuchi S, Seriu T, Bartram CR, Golub TR, Reiter A, Miyoshi I, Gilliland DG and Koeffler HP. . 1997 Leukemia 11: 1220–1223.

  • Tomasson MH, Sternberg DW, Williams IR, Carroll M, Cain D, Aster JC, Ilaria Jr RL, Etten RA and Gilliland DG. . 2000 J. Clin. Invest. 105: 423–432.

  • Tomasson MH, Williams IR, Hasserjian R, Udomsakdi C, McGrath SM, Schwaller J, Druker B and Gilliland DG. . 1999 Blood 93: 1707–1714.

  • Van Rompaey L, Dou W, Buijs A and Grosveld G. . 1999 Neoplasia 1: 526–536.

  • Wai DH, Knezevich SR, Lucas T, Jansen B, Kay RJ and Sorensen PH. . 2000 Oncogene 19: 906–915.

  • Wang L, Swat W, Fujiwara Y, Gilliland D, Golub T and Orkin S. . 1998 Genes Dev. 12: 2392–2402.

  • Wang LC, Kuo F, Fujiwara Y, Gilliland DG, Golub TR and Orkin SH. . 1997 EMBO J 16: 4374–4383.

  • Wasylyk B, Hagman J and Gutierrez-Hartmann A. . 1998 Trends Biochem. Sci. 23: 213–216.

  • Wasylyk C, Maira SM, Sobieszczuk P and Wasylyk B. . 1994 Oncogene 9: 3665–3673.

  • Wlodarska I, Marynen P, La Starza R, Mecucci C and Van den Berghe H. . 1996 Cytogenet Cell. Genet. 72: 229–235.

  • Xing X, Wang SC, Xia W, Zou Y, Shao R, Kwong KY, Yu Z, Zhang S, Miller S, Huang L and Hung MC. . 2000 Nat. Med. 6: 189–195.

  • Yagasaki F, Jinnai I, Yoshida S, Yokoyama Y, Matsuda A, Kusumoto S, Kobayashi H, Terasaki H, Ohyashiki K, Asou N, Murohashi I, Bessho M and Hirashima K. . 1999 Genes Chromosomes Cancer 26: 192–202.

  • Zindy F, Quelle DE, Roussel MF and Sherr CJ. . 1997 Oncogene 15: 203–211.

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Acknowledgements

The authors would like to thank Martine Roussel for providing the Ha-Ras/Lys12 retroviral construct, Elio Vanin for pSRα-VSV-G and pQE-Pam3-E retroviral vectors, Craig McPherson and A Hollenbach for preparing the pSRα-IRES-GFP retroviral vector, Christine Eischen and John Cleveland for extensive analysis of expression of cell cycle related proteins by Western blotting, Charlette Hill for secretarial assistance, Richard Ashmun for FACS analysis, Tom Curran for use of SZ×microscope and Wenkai Dou for technical assistance. This work was supported in part by NCl grant CA72999-03, the cancer center (CORE) support grant CA-21765, and by the American Lebanese Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital.

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

    L Van Rompaey, M Potter, C Adams & G Grosveld

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  1. L Van Rompaey
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Van Rompaey, L., Potter, M., Adams, C. et al. Tel induces a G1 arrest and suppresses Ras-induced transformation. Oncogene 19, 5244–5250 (2000). https://doi.org/10.1038/sj.onc.1203899

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