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:

Loss of c-abl facilitates anchorage-independent growth of p53- and RB- deficient primary mouse embryonic fibroblasts

Oncogene volume 23, pages 8527–8534 (2004)Cite this article

Abstract

The c-abl tyrosine kinase is the proto-oncogene of the v-abl oncogene of the Abelson murine leukemia virus. Although mutational variants of c-Abl can exhibit gain of function and can produce a transformed phenotype, the function of c-Abl in transformation remained unclear. Here, we report that the loss of c-abl facilitates transformation. c-abl-knockout mouse embryonic fibroblasts (MEFs) immortalized by SV40 T antigen acquired anchorage-independent growth, and by constructing mutational variants of T antigen we showed that binding of large T antigen to p53 and RB was necessary to induce anchorage-independent growth. Although c-abl/p53 double-knockout MEFs did not undergo anchorage-independent growth, those expressing human papilloma virus 16 E7, which mainly inactivates RB, did. Our results show that the loss of c-abl facilitates anchorage-independent growth in the context of p53 and RB deficiency, and suggest that loss of function of c-abl facilitates some types of transformation.

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

Similar content being viewed by others

References

  • Abelson HT and Rabstein LS . (1970). Cancer Res., 30, 2213–2222.

  • Akagi T, Sasai K and Hanafusa H . (2003). Proc. Natl. Acad. Sci. USA, 110, 13567–13572.

  • Ali SH and DeCaprio JA . (2001). Semin. Cancer Biol., 11, 15–23.

  • Asimakopoulos FA, Shteper PJ, Fibach E, Rachmilewitz E, Ben-Neriah Y and Ben-Yehuda D . (1999). Blood, 94, 1141.

  • Bear JE, Loureiro JJ, Libova I, Fassler R, Wehland J and Gertler FB . (2000). Cell, 101, 717–728.

  • Bikel I, Montano X, Agha ME, Brown M, McCormack M, Boltax J and Livingston DM . (1987). Cell, 48, 321–330.

  • DeCaprio JA, Ludlow JW, Figge J, Shew JY, Huang CM, Lee WH, Marsilio E, Paucha E and Livingston DM . (1988). Cell, 54, 275–283.

  • Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery Jr CA, Butel JS and Bradley A . (1992). Nature, 356, 215–221.

  • Fan PD and Goff SP . (2000). Mol. Cell. Biol., 20, 7591–7601.

  • Feshchenko EA, Shore SK and Tsygankov AY . (1999). Oncogene, 18, 3703–3715.

  • Gertler FB, Comer AR, Juang JL, Ahern SM, Clark MJ, Liebl EC and Hoffmann FM . (1995). Genes Dev., 9, 521–533.

  • Gertler FB, Niebuhr K, Reinhard M, Wehland J and Soriano P . (1996). Cell, 87, 227–239.

  • Goff SP, Gilboa E, Witte ON and Baltimore D . (1980). Cell, 22, 777–785.

  • Hahn WC, Dessain SK, Brooks MW, King JE, Elenbaas B, Sabatini DM, DeCaprio JA and Weinberg RA . (2002). Mol. Cell. Biol., 22, 2111–2123.

  • Hantschel O, Nagar B, Guettler S, Kretzschmar J, Dorey K, Kuriyan J and Superti-Furga G . (2003). Cell, 112, 845–857.

  • Hardin JD, Boast S, Mendelsohn M, de los Santos K and Goff SP . (1996). Oncogene, 12, 2669–2677.

  • Issa JP, Kantarjian H, Mohan A, O'Brien S, Cortes J, Pierce S and Talpaz M . (1999). Blood, 93, 2075–2080.

  • Jat PS and Sharp PA . (1986). J. Virol., 59, 746–750.

  • Jove R and Hanafusa H . (1987). Annu. Rev. Cell Biol., 3, 31–56.

  • Kain KH, Gooch S and Klemke RL . (2003). Oncogene, 22, 6071–6080.

  • Kalderon D and Smith AE . (1984). Virology, 139, 109–137.

  • Lane DP and Crawford LV . (1979). Nature, 278, 261–263.

  • Miyoshi-Akiyama T, Aleman LM, Smith JM, Adler CE and Mayer BJ . (2001). Oncogene, 20, 4058–4069.

  • Morita S, Kojima T and Kitamura T . (2000). Gene Ther., 7, 1063–1066.

  • Nagar B, Hantschel O, Young MA, Scheffzek K, Veach D, Bornmann W, Clarkson B, Superti-Furga G and Kuriyan J . (2003). Cell, 112, 859–871.

  • Pallas DC, Shahrik LK, Martin BL, Jaspers S, Miller TB, Brautigan DL and Roberts TM . (1990). Cell, 60, 167–176.

  • Pawlak G and Helfman DM . (2001). Curr. Opin. Genet. Dev., 11, 41–47.

  • Peden KW, Srinivasan A, Farber JM and Pipas JM . (1989). Virology, 168, 13–21.

  • Pendergast AM, Muller AJ, Havlik MH, Clark R, McCormick F and Witte ON . (1991). Proc. Natl. Acad. Sci. USA, 88, 5927–5931.

  • Pipas JM and Levine AJ . (2001). Semin. Cancer Biol., 11, 23–30.

  • Rundell K and Parakati R . (2001). Semin. Cancer Biol., 11, 5–13.

  • Sawyers CL, McLaughlin J, Goga A, Havlik M and Witte O . (1994). Cell, 77, 121–131.

  • Schwartzberg PL, Stall AM, Hardin JD, Bowdish KS, Humaran T, Boast S, Harbinson ML, Robertson EJ and Goff SP . (1991). Cell, 65, 1165–1175.

  • Scita G, Nordstrom J, Carbone R, Tenca P, Giardina G, Gutkind S, Bjarnegard M, Betsholtz C and Di Fiore PP . (1999). Nature, 401, 290–293.

  • Shishido T, Akagi T, Chalmers A, Maeda M, Terada T, Georgescu MM and Hanafusa H . (2001). Genes Cells, 6, 431–440.

  • Shishido T, Akagi T, Ouchi T, Georgescu MM, Langdon WY and Hanafusa H . (2000). Proc. Natl. Acad. Sci. USA, 97, 6439–6444.

  • Smith JM and Mayer BJ . (2002). Front Biosci., 7, d31–d42.

  • Tani K, Sato S, Sukezane T, Kojima H, Hirose H, Hanafusa H and Shishido T . (2003). J. Biol. Chem., 278, 21685–21692.

  • Todaro JG and Green H . (1963). J. Cell Biol., 17, 299–313.

  • Tybulewicz VL, Crawford CE, Jackson PK, Bronson RT and Mulligan RC . (1991). Cell, 65, 1153–1163.

  • Weinberg RA . (1985). Science, 230, 770–776.

  • Whang YE, Tran C, Henderson C, Syljuasen RG, Rozengurt N, McBride WH and Sawyers CL . (2000). Proc. Natl. Acad. Sci. USA, 97, 5486–5491.

  • Woodring PJ, Hunter T and Wang JY . (2003). J. Cell Sci., 116, 2613–2626.

  • Zion M, Ben-Yehuda D, Avraham A, Cohen O, Wetzler M, Melloul D and Ben-Neriah Y . (1994). Proc. Natl. Acad. Sci. USA, 91, 10722–10726.

Download references

Acknowledgements

We thank Ian Smith for critically reading our manuscript. We acknowledge Makiko Maeda and Toshie Terada for technical assistance. We are also grateful to Masuo Yutsudo, Toshio Kitamura, David Baltimore, Richard Mulligan, Stephan Feller, Sharon Boast and Feng Cong for reagents and help. T Shishido was a domestic research fellow of the Japan Science and Technology Corporation and the Japan Society for the Promotion of Science. This work was supported by a specially promoted research grant and a Grant-in-Aid for 21st Century COE Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, as well as a fund from Ono Pharmaceutical Co., Ltd. T Shishido was also supported by Osaka Cancer Research Foundation.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Oncology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka, 565-0874, Japan

    Jun Suzuki, Taiko Sukezane, Tsuyoshi Akagi, Mayumi Ohtani, Hidesaburo Hanafusa & Tomoyuki Shishido

  2. Laboratory of Molecular Oncology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, 630-0101, Japan

    Jun Suzuki & Tomoyuki Shishido

  3. Department of Molecular Oncology, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan

    Jun Suzuki & Taiko Sukezane

  4. Department of Molecular Genetics, Box-11, UT MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Maria Magdalena Georgescu

  5. Department of Microbiology, School of Medicine, Shiga University of Medical Science, Tsukinowa-cho, Otsu, Shiga, 520-2192, Japan

    Hirokazu Inoue

  6. Ludwig Institute for Cancer Research, London, WIW 7BS, UK

    Parmjit S Jat

  7. Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, 10032, NY, USA

    Stephen P Goff

Authors
  1. Jun Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Taiko Sukezane
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tsuyoshi Akagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Magdalena Georgescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mayumi Ohtani
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hirokazu Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Parmjit S Jat
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stephen P Goff
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hidesaburo Hanafusa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tomoyuki Shishido
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tomoyuki Shishido.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Suzuki, J., Sukezane, T., Akagi, T. et al. Loss of c-abl facilitates anchorage-independent growth of p53- and RB- deficient primary mouse embryonic fibroblasts. Oncogene 23, 8527–8534 (2004). https://doi.org/10.1038/sj.onc.1207894

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1207894

Keywords

This article is cited by

Search

Advanced search

Quick links