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:

Thyroid cell transformation requires the expression of the HMGA1 proteins

Oncogene volume 21, pages 2971–2980 (2002)Cite this article

Abstract

Elevated expression of HMGA1 and HMGA2 proteins is correlated with a highly malignant phenotype in several human tumors. We previously demonstrated that the block of HMGA2 protein synthesis prevented rat thyroid cell transformation by murine retroviruses. Suppression of HMGA2 synthesis was associated with lack of induction of HMGA1 proteins suggesting that both HMGA1 and HMGA2 play a role in the process of neoplastic transformation. To determine the role of the HMGA1 gene in thyroid cell transformation, we blocked HMGA1 protein synthesis by an antisense methodology. Here we report that transfection of an HMGA1 cDNA antisense construct into a normal rat thyroid cell line (FRTL-5 Cl2), followed by infection with Kirsten murine sarcoma virus (KiMSV), generated a transformed cell line that expresses high levels of the v-ras-Ki oncogene and that does not require thyroid-stimulating hormones for growth. However, this cell line does not show the malignant phenotype, i.e., it neither grows in soft agar nor induces tumors after injection in athymic mice. Moreover, the lack of the neoplastic phenotype in the virus-infected thyroid cells carrying the HMGA1 antisense construct correlates with the absence of induction of AP-1 transcriptional activity.

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
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

References

  • Abe N, Watanabe T, Sugiyama M, Chiappetta G, Fusco A, Atomi Y . 1999 Cancer Res. 59: 1169–1174

  • Abe N, Watanabe T, Masaki T, Mori T, Sugiyama M, Uchimura H, Fujioka Y, Chiappetta G, Fusco A, Atomi Y . 2000 Cancer Res. 60: 3117–3122

  • Ambesi-Impiombato FS, Parks LAM, Coon HG . 1980 Proc. Natl. Acad. Sci. USA 77: 3455–3459

  • Baldassarre G, Fedele M, Battista S, Vecchione A, Klein-Szanto AJ, Santoro M, Waldmann TA, Azimi N, Croce CM, Fusco A . 2001 Proc. Natl. Acad. Sci. USA 98: 7970–7975

  • Bandiera A, Bonifacio D, Manfioletti G, Mantovani F, Rustighi A, Zanconati F, Fusco A, Di Bonito L, Giancotti V . 1998 Cancer Res. 58: 426–431

  • Berlingieri MT, Manfioletti G, Santoro M, Bandiera A, Visconti R, Giancotti V, Fusco A . 1995 Mol. Cell. Biol. 15: 1545–1553

  • Berlingieri MT, Akamizu T, Fusco A, Grieco M, Colletta G, Cirafici AM, Ikuyama S, Kohn LD, Vecchio G . 1990 Biochem. Biophys. Res. Commun. 173: 172–178

  • Briggs MR, Kadonaga JT, Bell SP, Tjian R . 1986 Science 234: 47–52

  • Bustin M . 1999 Mol. Cell. Biol. 19: 5237–5246

  • Chiappetta G, Avantaggiato V, Visconti R, Fedele M, Battista S, Trapasso F, Merciai FM, Fidanza V, Giancotti V, Santoro M, Simeone A, Fusco A . 1996 Oncogene 13: 2439–2446

  • Chiappetta G, Bandiera A, Berlingieri MT, Visconti R, Manfioletti G, Battista S, Martinez-Tello FJ, Santoro M, Giancotti V, Fusco A . 1995 Oncogene 10: 1307–1314

  • Chiappetta G, Tallini G, De Biasio MC, Manfioletti G, Martines-Tello FJ, Pentimalli F, De Nigris F, Mastro A, Botti G, Fedele M, Bergen N, Santoro M, Giancotti V, Fusco A . 1998 Cancer Res. 58: 4193–4198

  • Chiappetta G, Manfioletti G, Pentimalli F, Abe N, Di Bonito M, Vento MT, Giuliano A, Fedele M, Viglietto G, Santoro M, Watanabe T, Giancotti V, Fusco A . 2001 Int. J. Cancer 91: 147–151

  • Cohen DR, Curran T . 1988 Mol. Cell. Biol. 8: 2063–2069

  • Di Lauro R, Obici S, Acquaviva A, Alvino C . 1982 Gene 19: 117–125

  • Fedele M, Bandiera A, Chiappetta G, Battista S, Viglietto G, Manfioletti G, Casamassimi A, Santoro M, Giancotti V, Fusco A . 1996 Cancer Res. 56: 1896–1901

  • Fedele M, Battista S, Kenyon L, Baldassarre G, Fidanza V, Klein-Szanto AJP, Parlow AF, Visone R, Pierantoni GM, Outwater F, Santoro M, Croce CM, Fusco A . 2002 Oncogene 21: in press

  • Fedele M, Pierantoni GM, Berlingieri MT, Battista S, Baldassarre G, Munshi N, Dentice M, Thanos D, Santoro M, Viglietto G, Fusco A . 2001a Cancer Res. 61: 4583–4590

  • Fedele M, Battista S, Manfioletti G, Croce CM, Giancotti V, Fusco A . 2001b Carcinogenesis 22: 101–109

  • Fusco A, Berlingieri MT, Di Fiore PP, Portella G, Grieco M, Vecchio G . 1987 Mol. Cell. Biol. 7: 3365–3370

  • Gack S, Vallon R, Schaper J, Ruther U, Angel P . 1994 J. Biol. Chem. 269: 363–369

  • Giancotti V, Berlingieri MT, Di Fiore PP, Fusco A, Vecchio G, Crane-Robinson C . 1985 Cancer Res. 45: 6051–6057

  • Giancotti V, Pani B, D'Andrea P, Berlingieri MT, Di Fiore PP, Fusco A, Vecchio G, Philp R, Crane-Robinson C, Nicolas RH, Wright CA, Goodwin GH . 1987 EMBO J. 6: 1981–1987

  • Giancotti V, Buratti E, Perissin L, Zorzet S, Balmain A, Portella G, Fusco A, Goodwin GH . 1989 Exp. Cell. Res. 184: 538–545

  • Graham FL, Van der Eb AJ . 1973 Virology 52: 456–467

  • Johnson KR, Lehn DA, Reeves R . 1989 Mol. Cell. Biol. 9: 2114–2123

  • Lee W, Mitchell P, Tjian R . 1987 Cell 49: 741–752

  • Lovell-Badge R . 1995 Nature 376: 725–726

  • Macpherson I, Montagnier I . 1964 Virology 23: 291–294

  • Manfioletti G, Giancotti V, Bandiera A, Buratti E, Sautiere P, Cary P, Crane-Robinson C, Coles B, Goodwin GH . 1991 Nucleic Acids Res. 19: 6793–6797

  • Melillo RM, Pierantoni GM, Scala S, Battista S, Fedele M, Stella A, De Biasio MC, Chiappetta G, Fidanza V, Condorelli G, Santoro M, Croce CM, Viglietto G, Fusco A . 2001 Mol. Cell. Biol. 21: 2485–2495

  • Reeves R, Edberg DD, Li Y . 2001 Mol. Cell. Biol. 21: 575–594

  • Ryder K, Lau LF, Nathans D . 1988 Proc. Natl. Acad. Sci. USA 85: 1487–1491

  • Sambrook J, Fritsch EF, Maniatis T . 1989 Molecular Cloning: A Laboratory Manual Cold Spring Harbor (NY) Second Edition New York: Cold Spring Harbor Laboratory Press

    Google Scholar 

  • Scala S, Portella G, Fedele M, Chiappetta G, Fusco A . 2000 Proc. Natl. Acad. Sci. USA 97: 4256–4261

  • Scala S, Portella G, Vitagliano D, Ledent C, Chiappetta G, Giancotti V, Dumont J, Fusco A . 2001 Carcinogenesis 22: 251–256

  • Tamimi Y, van der Poel HG, Denyn MM, Umbas R, Karthaus HFM, Debruyne FMJ, Shalken JA . 1993 Cancer Res. 53: 5512–5516

  • Tokunaga K, Nakamura Y, Sakataka K, Fujimari K, Ohkuba M, Sawada K, Sakiyama S . 1987 Cancer Res. 21: 5616–5619

  • Vallone D, Battista S, Pierantoni GM, Fedele M, Casalino L, Santoro M, Viglietto G, Fusco A, Verde P . 1997 EMBO J. 16: 5310–5321

  • Wood LJ, Mukherjee M, Dolde CE, Xu Y, Maher JF, Bunton TE, Williams JB, Resar LM . 2000a Mol. Cell. Biol. 20: 5490–5502

  • Wood LJ, Maher JF, Bunton TE, Resar LM . 2000b Cancer Res. 60: 4256–4261

  • Zannini MS, Francis-Lang H, Plachov D, Di Lauro R . 1992 Mol. Cell. Biol. 12: 4230–4241

  • Zhou X, Benson KF, Ashar HR, Chada K . 1995 Nature (Lond.) 376: 771–774

Download references

Acknowledgements

This work was supported by grants from ‘Progetto Speciale Oncosoppressori’ AIRC, the Progetto Finalizzato ‘Biotecnologie’ of the Consiglio Nazionale delle Ricerche (CNR), CNE Progetto ‘5%’, the MURST project ‘Terapie antineoplastiche innovative’, the ‘Ministero della Sanità’, the Università degli Studi di Trieste (60%), the Ministero della Ricerca Scientifica e Tecnologica (40%). We are grateful to Jean Ann Gilder for text editing.

Author information

Authors and Affiliations

  1. Centro di Endocrinologia ed Oncologia Sperimentale del Consiglio Nazionale delle Ricerche c/o Dipartimento di Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli, Via Pansini 5, Naples, 80131, Italy

    Maria Teresa Berlingieri, Giovanna M Pierantoni, Massimo Santoro & Alfredo Fusco

  2. Dipartimento di Biochimica, Biofisica e Chimica delle Macromolecole, University of Trieste, Italy

    Vincenzo Giancotti

Authors
  1. Maria Teresa Berlingieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovanna M Pierantoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vincenzo Giancotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Massimo Santoro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alfredo Fusco
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alfredo Fusco.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berlingieri, M., Pierantoni, G., Giancotti, V. et al. Thyroid cell transformation requires the expression of the HMGA1 proteins. Oncogene 21, 2971–2980 (2002). https://doi.org/10.1038/sj.onc.1205368

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205368

Keywords

This article is cited by

Search

Advanced search

Quick links