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Identification of IGFBP-6 as a significantly downregulated gene by β-catenin in desmoid tumors

Oncogene volume 23, pages 654–664 (2004)Cite this article

Abstract

Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors in which β-catenin-mediated TCF-3-dependent transcription is activated. To provide more insight into the pathophysiology of these tumors, expression profiles were generated using oligonucleotide arrays (Affymetrix). In total, 69 differentially expressed genes were identified in desmoids compared to normal fibroblasts (fascia) from the same patients. The differential expression of a selection of genes was confirmed using RT–PCR and Northern blotting. We further evaluated the insulin-like growth factor-binding protein 6 (IGFBP-6), a gene that was consistently downregulated in all desmoids tested. Promotor studies and electromobility shift assays revealed two functional β-catenin/TCF-responsive elements in the human IGFBP-6 promoter. These findings suggest that IGFBP-6 is directly downregulated by the β-catenin/TCF complex in desmoid tumors, and imply a role for the IGF axis in the proliferation of desmoid tumors.

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References

  • Albuquerque C, Breukel C, van der Luijt R, Fidalgo P, Lage P, Slors FJM, Leitao CN, Fodde R and Smits R . (2000). Hum. Mol. Genet., 11, 1549–1560.

  • Alman BA, Li C, Pajerski ME, Diaz-Cano S and Wolfe HJ . (1997). Am. J. Pathol., 151, 329–334.

  • Bach LA . (1999). Horm. Metab. Res., 31, 226–234.

  • Bauer A, Chauvet S, Huber O, Usseglio F, Rothbacher U, Aragnol D, Kemler R and Pradel J . (2000). EMBO J., 19, 6121–6130.

  • Brannon M, Gomperts M, Sumoy L, Moon RT and Kimelman D . (1997). Genes Dev., 11, 2359–2370.

  • Cadigan KM and Nusse R . (1997). Genes Dev., 11, 3286–3305.

  • Cheon SS, Cheah AYL, Turley S, Nadean P, Poon R, Clevers H and Alman BA . (2002). Proc. Natl. Acad. Sci. USA, 99, 6973–6978.

  • Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh CL and Feinberg AP . (2002). Cancer Res., 62, 6442–6446.

  • Cullen KJ, Lippman ME, Chow D, Hill S, Rosen N and Zwiebel JA . (1992). Mol. Endocrinol., 6, 991–1000.

  • de Moor CH, Jansen M, Bonte EJ, Thomas AA, Sussenbach JS and Van Den Brande JL . (1995). Biochem. J., 307, 225–231.

  • Eccles DM, VanderLuijt R, Breukel C, Bullman H, Bunyan D, Fisher A, Barber J, duBoulay C, Pimrose J, Burn J and Fodde R . (1996). Am. J. Hum. Genet., 59, 1193–1201.

  • Fujita M, Furukawa Y, Nagasawa Y, Ogawa M and Nakamura Y . (2000). Cancer Res., 60, 6683–6687.

  • Gat U, DasGupta R, Degenstein L and Fuchs E . (1998). Cell, 95, 605–614.

  • He T, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa L, Morin PJ, Vogelstein B and Kinzler K . (1998). Science, 281, 1509–1512.

  • Hecht A and Kemler R . (2000). EMBO Rep., 1, 24–28.

  • Kielman MF, Rindapaa M, Gaspar C, van Poppel N, Breukel C, van Leeuwen S, Taketo MM, Roberts S, Smits R and Fodde R . (2002). Nat. Genet., 32, 594–605.

  • Kim EJ, Kang YH, Schaffer BS, Bach LA, MacDonald RG and Park JHY . (2002). J. Cell Physiol., 190, 92–100.

  • Li C, Bapat B and Alman BA . (1998). Am. J. Pathol., 153, 709–714.

  • Morin P, Sparks A, Korinek V, Barker N, Clevers H, Vogelstein B and Kinzler K . (1997). Science, 275, 1787–1790.

  • Poon R, Smits R, Li C, Jagmohan-Changur S, Kong M, Cheon S, Yu C, Fodde R and Alman BA . (2000). Oncogene, 20, 451–460.

  • Roghani M, Segovia B, Whitechurch O and Binoux M . (1991). Growth Regul., 3, 125–130.

  • Roose J and Clevers H . (1999). Biochim. Biophys. Acta, 142, M23–M37.

  • Roose J, Molenaar M, Peterson J, Hurenkamp J, Brantjes H, Moerer P, van de Wetering M, Destree O and Clevers H . (1998). Nature, 395, 608–612.

  • Saito T, Yoshinao O, Kazuhiro T, Matsuda S, Tamiya S and Iwamoto Y . (2001). J. Pathol., 195, 222–228.

  • Singh P, Dai B, Yallampalli C and Xu Z . (1994). Am. J. Physiol., 267, G608–G617.

  • Tejpar S, Li C, Yu C, Poon R, Denys H, Sciot R, Van Cutsem E, Cassiman JJ and Alman B . (2001). Br. J. Cancer, 85, 98–101.

  • Tejpar S, Nollet F, Li C, Wunder JS, Michils G, Dal Cin P, Van Cutsem E, Bapat B, Van Roy F, Cassiman JJ and Alman BA . (1999). Oncogene, 18, 6615–6620.

  • Zhang L, Zhou W, Velculescu VE, Kern SE, Hubran RH, Hamilton SR, Vogelstein B and Kinzler KW . (1997). Science, 276, 1268–1272.

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Acknowledgements

The following investigators generously provided plasmids: Dr D Strong (p1731luc), Dr B Vogelstein (S33 β-catenin), Dr P Polakis (delta N89 β-catenin); Dr F Dc Cormick (dnTCF). We thank Professor I De Wever, Professor R Sciot and Professor D Uyttendaele for providing samples, Professor R Winkler for the IGFII protein assays and Dr K Verschueren for technical assistance with the EMSA experiments. H Denys is a fellow of the Fund for Scientific Research-Flanders (FSR). A Jadidizadeh and S Amini Nik are supported by the Iranian Ministry of Health and Medical Education. BA Alman is supported by the Canadian Research Chairs Program. This work was funded by grant G.033.02 from ‘Kom op Tegen Kanker’, Fund for Scientific Research-Flanders, Belgium, by grant I.32.2000.F-13 from the Belgian Federation Against Cancer, and by the National Cancer Institute of Canada.

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Authors and Affiliations

  1. Center for Human Genetics, University of Leuven, Leuven, B-3000, Belgium

    Hannelore Denys, Ali Jadidizadeh, Saeid Amini Nik, Kim Van Dam, Jean-Jacques Cassiman & Sabine Tejpar

  2. Department of Electrical Engineering, University of Leuven, Leuven, B-3001, Belgium

    Stein Aerts

  3. The Program in Developmental Biology, The Hospital for Sick Children and the University of Toronto, Toronto, M5G1X8, Ontario, Canada

    Benjamin A Alman

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  1. Hannelore Denys
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  2. Ali Jadidizadeh
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Correspondence to Sabine Tejpar.

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Denys, H., Jadidizadeh, A., Amini Nik, S. et al. Identification of IGFBP-6 as a significantly downregulated gene by β-catenin in desmoid tumors. Oncogene 23, 654–664 (2004). https://doi.org/10.1038/sj.onc.1207160

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