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  • Original Paper
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Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumors

Abstract

The presence of putative tumor-suppressor genes on chromosome 16q23.2-24.1 has been suggested by LOH analysis in several cancer types. This region overlaps with the fragile site FRA16D and the region of homozygous deletions found in several cancer types. The candidate gene WWOX/FOR has been mapped within this region. The mouse homologue of the WWOX protein has been defined as an apoptogenic protein and an essential partner of p53 in cell death, supporting WWOX as a tumor suppressor gene candidate. We performed an expression study of the WWOX/FOR gene in a series of human breast tumors and breast cancer cell lines, and detected reduced expression of the WWOX/FOR transcript in a series of breast cancer cells. Furthermore, identification of two distinct alternative WWOX transcripts expressed at high levels in human tumors suggests an involvement of the WWOX gene in breast cancer progression.

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Abbreviations

LOH:

loss of heterozygosity

PAC:

P1-derived artificial chromosome

EST:

expressed sequence tag

ADH:

alcohol dehydrogenase

References

  • Aldaz CM, Chen T, Sahin A, Cunningham J, Bondy M . 1995 Cancer Res. 55: 3976–3981

  • Bednarek AK, Laflin KJ, Daniel RL, Liao Q, Hawkins KA, Aldaz CM . 2000 Cancer Res. 60: 2140–2145

  • Bieche I, Lidereau R . 1995 Genes Chromosomes Cancer 14: 227–251

  • Bieche I, Lidereau R . 1999 Cancer Res. 59: 2546–2550

  • Chang NS, Pratt N, Heath J, Schultz L, Sleve D, Carey GB, Zevotek N . 2001 J. Biol. Chem. 276: 3361–3370

  • Chesi M, Bergsagel PL, Shonukan OO, Martelli ML, Brents LA, Chen T, Schrock E, Ried T, Kuehl WM . 1998 Blood 91: 4457–4463

  • Chomczynski P, Sacchi N . 1987 Anal Biochem. 162: 156–159

  • Cleton-Jansen AM, Moerland EW, Kuipers-Dijkshoorn NJ, Callen DF, Sutherland GR, Hansen B, Devilee P, Cornelisse C . 1994 Genes Chromosomes Cancer 9: 101–107

  • Davidson JM, Gorringe KL, Chin SF, Orsetti B, Besret C, Courtay-Cahen C, Roberts I, Theillet C, Caldas C, Edwards PA . 2000 Br. J. Cancer 83: 1309–1317

  • Deng G, Chen L, Schott D, Thor A, Bhargava V, Ljung B, Chew K, Smith H . 1994 Cancer Res. 54: 499–505

  • Dorion-Bonnet F, Mautalenn S, Hostein I, Longy M . 1995 Genes Chromosomes Cancer 14: 171–181

  • Driouch K, Briffod M, Champeme MH, Lidereau R . 1998 Cancer Res. 58: 2081–2086

  • Driouch K, Dorion-Bonnet F, Briffod M, Champeme MH, Longy M, Lidereau R . 1997 Genes Chromosomes Cancer 19: 185–191

  • Elo JP, Harkonen P, Kyllonen AP, Lukkarinen O, Poutanen M, Vihko R, Vihko P . 1997 Cancer Res. 57: 3356–3359

  • Frengen E, Zhao B, Howe S, Weichenhan D, Osoegawa K, Gjernes E, Jessee J, Prydz H, Huxley C, de Jong PJ . 2000 Genomics 68: 118–126

  • Grundy RG, Pritchard J, Scambler P, Cowell JK . 1998 Br. J. Cancer 78: 1181–1187

  • Ioannou PA, Amemiya CT, Garnes J, Kroisel PM, Shizuya H, Chen C, Batzer MA, de Jong PJ . 1994 Nat. Genet. 6: 84–89

  • Krummel KA, Roberts LR, Kawakami M, Glover TW, Smith DI . 2000 Genomics 69: 37–46

  • Larsen F, Gundersen G, Prydz H . 1992 Genet. Anal. Tech. Appl. 9: 80–85

  • Larsson C, Byström C, Skoog L, Rotstein S, Nordenskjöld M . 1990 Genes Chromosomes Cancer 2: 191–197

  • Latif F, Fivash M, Glenn G, Tory K, Orcutt ML, Hampsch K, Delisio J, Lerman M, Cowan J, Beckett M, Weichselbaum R . 1992 Cancer Res. 52: 1451–1456

  • Latil A, Cussenot O, Fournier G, Driouch K, Lidereau R . 1997 Cancer Res. 57: 1058–1062

  • Li C, Berx G, Larsson C, Auer G, Aspenblad U, Pan Y, Sundelin B, Ekman P, Nordenskjold M, van Roy F, Bergerheim USR . 1999 Genes Chromosomes Cancer 24: 175–182

  • Lindblom A, Rotstein S, Stoog L, Nordenskjöld M, Larson C . 1993 Cancer Res. 53: 3707–3711

  • Mangelsdorf M, Ried K, Woollatt E, Dayan S, Eyre H, Finnis M, Hobson L, Nancarrow J, Venter D, Baker E, Richards RI . 2000 Cancer Res. 60: 1683–1689

  • Mashimo T, Watabe M, Cuthbert AP, Newbold RF, Rinker-Schaeffer CW, Helfer E, Watabe K . 1998 Cancer Res. 58: 4572–4576

  • Osoegawa K, Mammoser AG, Wu C, Frengen E, Zeng C, Catanese JJ, de Jong PJ . 2001 Genome Res. 11: 483–496

  • Paige AJ, Taylor KJ, Stewart A, Sgouros JG, Gabra H, Sellar GC, Smyth JF, Porteous DJ, Watson JE . 2000 Cancer Res. 60: 1690–1697

  • Paige AJ, Taylor KJ, Taylor C, Hillier SG, Farrington S, Scott D, Porteous DJ, Smyth JF, Gabra H, Watson JE . 2001 Proc. Natl. Acad. Sci. USA 98: 11417–11422

  • Ried K, Finnis M, Hobson L, Mangelsdorf M, Dayan S, Nancarrow JK, Woollatt E, Kremmidiotis G, Gardner A, Venter D, Baker E, Richards RI . 2000 Hum. Mol. Genet. 9: 1651–1663

  • Sato T, Akiyama F, Satamoko G, Kasumi F, Nakamura Y . 1991 Cancer Res. 51: 5794–5799

  • Shen Y, Kozman HM, Thompson A, Phillips HA, Holman K, Nancarrow J, Lane S, Chen LZ, Apostolou S, Doggett NA, Callen DF, Mulley JC, Sutherland GR, Richards RI . 1994 Genomics 22: 68–76

  • Skirnisdottir S, Eiriksdottir G, Baldursson T, Barkardottir RB, Egilsson V, Ingvarsson S . 1995 Int. J. Cancer 64: 112–116

  • Suzuki H, Komiya A, Emi M, Kuramochi H, Shiraishi T, Yatani R, Shimazaki J . 1996 Genes Chromosomes Cancer 17: 225–233

  • Takita K, Sato T, Miyagi M, Watatani M, Akiyama F, Sakamoto G, Kasumi F, Abe R, Nakamura Y . 1992 Cancer Res. 52: 3914–3917

  • Tsuda H, Callen DF, Fukutomi T, Nakamura Y, Hirohashi S . 1994 Cancer Res. 54: 513–517

  • Tsuda H, Zhang WD, Shimosato Y, Yokota J, Terada M, Sugimura T, Miyamura T, Hirohashi S . 1990 Proc. Natl. Acad. Sci. USA 87: 6791–6794

  • Watson JE, Gabra H, Taylor KJ, Rabiasz GJ, Morrison H, Perry P, Smyth JF, Porteous DJ . 1999 Genome Res. 9: 226–233

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Acknowledgements

We are indebted to the medical and surgical departments of the Centre René Huguenin for their cooperation, and to J Solheim and H Harstad for excellent technical assistance. This work was supported by the Ligue Nationale de Lutte Contre le Cancer (LNCC); the Association pour la Recherche sur le Cancer (ARC), the Research Council of Norway and the Norwegian Cancer Society (EF and HP). K Driouch was supported by a grant from the Ligue Nationale de Lutte Contre le Cancer.

The sequence data described in this paper have been submitted to the GenBank data library under accession numbers AW874683-AW874700, AZ124367-AZ124379, AZ124382.

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Correspondence to Keltouma Driouch or Eirik Frengen.

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Driouch, K., Prydz, H., Monese, R. et al. Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumors. Oncogene 21, 1832–1840 (2002). https://doi.org/10.1038/sj.onc.1205273

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