Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Expression of the wild-type insulin-like growth factor II receptor gene suppresses growth and causes death in colorectal carcinoma cells

Oncogene volume 18, pages 4063–4068 (1999)Cite this article

Abstract

The insulin-like growth factor II receptor (IGFIIR) has been implicated as a tumor suppressor gene in human malignancy. Frequent mutation, loss of heterozygosity, and microsatellite instability (MSI) directly affecting the IGFIIR gene have been reported in several primary human tumor types. However, to our knowledge, dynamic functional evidence of a growth-suppressive role for IGFIIR has not yet been provided. We identified one MSI-positive colorectal carcinoma cell line, SW48, with monoallelic mutation in IGFIIR identical to that seen in primary colorectal carcinomas. A zinc-inducible construct containing the wild-type IGFIIR cDNA was stably transfected into SW48 cells. Growth rate and apoptosis were compared between zinc-treated, untreated, and untransfected cells. A twofold increase in IGFIIR protein expression was detected after zinc treatment in discrete clonal isolates of transfected SW48 cells. Moreover, zinc induction of exogenous wild-type IGFIIR expression reproducibly decreased growth rate and increased apoptosis. These data prove that wild-type IGFIIR functions as a growth suppressor gene in colorectal cancer cells and provide dynamic in vitro functional support for the hypothesis that IGFIIR is a human growth suppressor gene.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Boynton RF, Huang Y, Blount PL, Reid BJ, Raskind WH, Haggitt RC, Newkirk C, Resau JH, Yin J, McDaniel T and Meltzer SJ. . 1991 Cancer Res. 51: 5766–5769.

  • Branch P, Hampson R and Karran P. . 1995 Cancer Res. 55: 2304–2309.

  • Culouscou JM, Remacle-Bonnet M, Garrouste F, Marvaldi J and Pommier G. . 1990 J. Cell Physiol. 143: 405–415.

  • Dahms NM and Brszycki-Wessel MA. . 1995 Arch. Biochem. Biophys. 317: 497–503.

  • De Souza AT, Hankins GR, Washington MK, Fine RL, Orton TC and Jirtle RL. . 1995a Oncogene 10: 1725–1729.

  • De Souza AT, Hankins GR, Washington MK, Orton TC and Jirtle RL. . 1995b Nature Genet. 11: 447–449.

  • Dennis PA and Rifkin DB. . 1991 Proc. Natl. Acad. Sci. USA 8: 580–584.

  • Devilee P, van Vliet M, van Sloun P, Kuipers Dijkshoorn N, Hermans J, Pearson PL and Cornelisse CJ. . 1991 Oncogene 6: 1705–1711.

  • Ellis MJC, Leav BA, Yang Z, Rasmussen A, Pearce A, Zweibel JA, Lippman ME and Cullen KJ. . 1996 Mol. Endo. 10: 286–297.

  • Guo YS, Jin GF, Townsend Jr CM, Zhang T, Sheng HM, Beauchamp RD and Thompson JC. . 1995 J. Am. Coll. Surg. 181: 145–154.

  • Hankins GR, De Souza AT, Bentley RC, Patel MR, Marks JR, Iglehart JD and Jirtle RL. . 1996 Oncogene 12: 2003–2009.

  • Herskowitz I. . 1987 Nature 329: 219–222.

  • Ko LJ and Prives C. . 1996 Genes Dev. 10: 1054–1072.

  • Kojima S, Nara K and Rifkin DB. . 1993 J. Cell Biol. 121: 439–448.

  • Kornfeld S. . 1992 Annu. Rev. Biochem. 61: 307–330.

  • Kyle JW, Nolan CM, Oshima A and Sly WS. . 1988 J. Biol. Chem. 263: 16230–16235.

  • Lamonerie T, Lavialle C, Haddada H and Brison O. . 1995 Int. J. Cancer. 61: 587–592.

  • Lau MM, Stewardt CE, Liu Z, Bhatt H, Rotwein P and Stewart CL. . 1994 Genes Dev. 8: 2953–2963.

  • Laureys G, Barton DE, Ullrich A and Francke U. . 1988 Genomics 3: 224–229.

  • Manni A, Badger B, Wei L, Zaenglein A, Grove R, Khin S, Heitjan D, Shimasake S and Ling N. . 1994 Cancer Res. 54: 2934–2942.

  • Markowitz S, Wang J, Myeroff L, Parsons R, Sun LZ, Lutterbaugh J, Fan RS, Zborowska E, Kinzler KW, Vogelstein B, Brattain M and Wilson JKV. . 1995 Science 268: 1336–1338.

  • Massague J. . 1990 Annu. Rev. Cell Biol. 6: 597–641.

  • Millikin D, Meese E, Vogelstein B, Witkowski C and Trent J. . 1991 Cancer Res. 51: 5449–5453.

  • Minniti CP, Tsokos M, Newton Jr WA and Helman LJ. . 1994 Am. J. Clin. Pathol. 101: 198–203.

  • Morgan DO, Edman JC, Standring DN, Fried VA, Smith MC, Roth RA and Rutter WJ. . 1987 Nature 329: 301–307.

  • Oka Y, Rozed LM and Czech MP. . 1985 J. Biol. Chem. 260: 9435–9442.

  • Ouyang H, Shiwaku H, Hagiwara H, Miura K, Abe T, Kato Y, Ohtani H, Shiiba K, Souza RF, Meltzer SJ and Horii A. . 1997 Cancer Res. 57: 1851–1854.

  • Parrizas M, Saltiel AR and LeRoith D. . 1997 J. Biol. Chem. 272: 154–161.

  • Parsons R, Myeroff LL, Liu B, Wilson JKV, Markowitz SD, Kinzler KW and Vogelstein B. . 1995 Cancer Res. 55: 5548–5550.

  • Rainier S, Dobry CJ and Feinberg AP. . 1995 Cancer Res. 55: 1836–1838.

  • Resnicoff M, Burgaud JL, Rotman HL, Abraham D and Baserga R. . 1995 Cancer Res. 55: 3739–3741.

  • Robertson GP, Coleman AB and Lugo TG. . 1996 Cancer Res. 56: 1635–1641.

  • Saito S, Saito H, Koi S, Sagae S, Kudo R, Saito J, Noda K and Nakamura Y. . 1992 Cancer Res. 52: 5815–5817.

  • Singleton JR, Dixit VM and Feldman EL. . 1996 J. Biol. Chem. 271: 31791–31794.

  • Souza RF, Appel R, Yin J, Wang S, Smolinski KN, Abraham JM, Zou TT, Shi YQ, Lei J, Cottrell J, Cymes K, Biden K, Simms L, Leggett B, Lynch PM, Frazier M, Powell SM, Harpaz N, Sugimura H, Young J and Meltzer SJ. . 1996 Nature Genet. 14: 255–257.

  • Souza RF, Lei J, Yin J, Appel R, Zou T-T, Zhou X-L, Wang S, Rhyu M-G, Cymes K, Chan O, Park W-S, Krasna MJ, Greenwald BD, Cottrell J, Abraham JM, Simms L, Leggett B, Young J, Harpaz N and Meltzer SJ. . 1997 Gastroenterology 112: 40–45.

  • Trent JM, Stanbridge EJ, McBride HL, Meese EU, Casey G, Araujo DE, Witkowski CM and Nagle RB. . 1990 Science 247: 568–571.

  • Wang S, Souza RF, Kong D, Yin J, Smolinski KN, Zou T-T, Frank T, Young J, Flanders K, Sugimura H, Abraham JM and Meltzer SJ. . 1997 Cancer Res. 57: 2543–2546.

  • Yun K, Molenaar AJ, Fiedler AM, Mark AJ, Eccles MR, Becroft DM and Reeve AE. . 1993 Lab. Invest. 69: 603–615.

Download references

Acknowledgements

Supported by USPHS grants CA67497, CA78843, CA77057, DK47717, the Robert and Sally D Funderburg Award, and the Office of Medical Research, Department of Veterans Affairs. RF Souza is the recipient of a Mentored Clinical Scientist Award (KO8-CA73782).

Author information

Authors and Affiliations

  1. Department of Medicine (GI Division), Dallas VA Medical Center and University of Texas-Southwestern Medical School, Dallas, Texas, 75216, TX, USA

    Rhonda F Souza

  2. Department of Medicine (GI Division), University of Maryland School of Medicine and VA Maryland Healthcare System, Baltimore, Maryland, USA

    Suna Wang, Kara N Smolinski, Jing Yin, Tong-Tong Zou, Dehe Kong, John M Abraham & Stephen J Meltzer

  3. Department of Greenebaum Cancer Center, University of Maryland School of Medicine and VA Maryland Healthcare System, Baltimore, Maryland, USA

    John M Abraham, Jeffrey A Toretsky & Stephen J Meltzer

  4. Department of Molecular and Cell Biology Graduate Program, University of Maryland School of Medicine and VA Maryland Healthcare System, Baltimore, Maryland, USA

    Kara N Smolinski, Dehe Kong, Jeffrey A Toretsky & Stephen J Meltzer

  5. Department of Pediatric Hematology-Oncology, University of Maryland School of Medicine and VA Maryland Healthcare System, Baltimore, Maryland, USA

    Manjusha Thakar & Jeffrey A Toretsky

Authors
  1. Rhonda F Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suna Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Manjusha Thakar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kara N Smolinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jing Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tong-Tong Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dehe Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. John M Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jeffrey A Toretsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Stephen J Meltzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Souza, R., Wang, S., Thakar, M. et al. Expression of the wild-type insulin-like growth factor II receptor gene suppresses growth and causes death in colorectal carcinoma cells. Oncogene 18, 4063–4068 (1999). https://doi.org/10.1038/sj.onc.1202768

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1202768

Keywords

This article is cited by

Search

Advanced search

Quick links