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.

  • Short Report
  • Published:

Ras and Myc can drive oncogenic cell proliferation through individual D-cyclins

Oncogene volume 24, pages 7114–7119 (2005)Cite this article

Abstract

D-type cyclins serve as cell cycle recipients of several oncogenic pathways. The specific sequences of the promoters of the cyclin D genes are thought to render particular D-cyclins responsive to specific oncogenic pathways. For instance, the Ras oncogene was postulated to signal through cyclin D1, while Myc can impact the cell cycle machinery by transcriptionally upregulating cyclin D2. In the current study we engineered mouse fibroblasts to express only cyclin D1, only D2, or only D3. These ‘single-cyclin’ cells allowed us to rigorously test the ability of cyclin D1, D2, or D3, when expressed on their own, to serve as recipients of the Ras- and Myc-driven oncogenic pathways. We found that each of the D-cyclins was sufficient to drive oncogenic proliferation of mouse fibroblasts. This, together with our recent observations that cells lacking all three D-cyclins show greatly reduced susceptibility to the oncogenic action of Ras and Myc, reveals that the Ras and Myc oncogenes can impact the core cell cycle machinery through all three D-cyclins.

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 4
Figure 3

Similar content being viewed by others

References

  • Albanese C, Johnson J, Watanabe G, Eklund N, Vu D, Arnold A and Pestell RG . (1995). J. Biol. Chem., 270, 23589–23597.

  • Albanese C, Wu K, D'Amico M, Jarrett C, Joyce D, Hughes J, Hulit J, Sakamaki T, Fu M, Ben-Ze'ev A, Bromberg JF, Lamberti C, Verma U, Gaynor RB, Byers SW and Pestell RG . (2003). Mol. Biol. Cell, 14, 585–599.

  • Alt JR, Cleveland JL, Hannink M and Diehl JA . (2000). Genes Dev., 14, 3102–3114.

  • Amanatullah DF, Zafonte BT, Albanese C, Fu M, Messiers C, Hassell J and Pestell RG . (2001). Methods Enzymol., 333, 116–127.

  • Balasenthil S, Sahin AA, Barnes CJ, Wang RA, Pestell RG, Vadlamudi RK and Kumar R . (2004). J. Biol. Chem., 279, 1422–1428.

  • Bartkova J, Lukas J, Strauss M and Bartek J . (1998). Oncogene, 17, 1027–1037.

  • Bouchard C, Dittrich O, Kiermaier A, Dohmann K, Menkel A, Eilers M and Luscher B . (2001). Genes Dev., 15, 2042–2047.

  • Bouchard C, Marquardt J, Bras A, Medema RH and Eilers M . (2004). EMBO J., 23, 2830–2840.

  • Bouchard C, Thieke K, Maier A, Saffrich R, Hanley-Hyde J, Ansorge W, Reed S, Sicinski P, Bartek J and Eilers M . (1999). EMBO J., 18, p5321–p5333.

  • Cheng M, Sexl V, Sherr CJ and Roussel MF . (1998). Proc. Natl. Acad. Sci. USA, 95, 1091–1096.

  • Ciemerych MA, Kenney AM, Sicinska E, Kalaszczynska I, Bronson RT, Rowitch DH, Gardner H and Sicinski P . (2002). Genes Dev., 16, 3277–3289.

  • Coller HA, Grandori C, Tamayo P, Colbert T, Lander ES, Eisenman RN and Golub TR . (2000). Proc. Natl. Acad. Sci. USA, 97, 3260–3265.

  • Dey A, She H, Kim L, Boruch A, Guris DL, Carlberg K, Sebti SM, Woodley DT, Imamoto A and Li W . (2000). Mol. Biol. Cell, 11, 3835–3848.

  • Diehl JA, Cheng M, Roussel MF and Sherr CJ . (1998). Genes Dev., 12, 3499–3511.

  • Dufourny B, van Teeffelen HA, Hamelers IH, Sussenbach JS and Steenbergh PH . (2000). J. Endocrinol., 166, 329–338.

  • Fantl V, Stamp G, Andrews A, Rosewell I and Dickson C . (1995). Genes Dev., 9, 2364–2372.

  • Filmus J, Robles AI, Shi W, Wong MJ, Colombo LL and Conti CJ . (1994). Oncogene, 9, 3627–3633.

  • Friedrichsen BN, Richter HE, Hansen JA, Rhodes CJ, Nielsen JH, Billestrup N and Moldrup A . (2003). Mol. Endocrinol., 17, 945–958.

  • Geng Y, Yu Q, Sicinska E, Das M, Schneider JE, Bhattacharya S, Rideout WM, Bronson RT, Gardner H and Sicinski P . (2003). Cell, 114, 431–443.

  • Hsia CY, Cheng S, Owyang AM, Dowdy SF and Liou HC . (2002). Int. Immunol., 14, 905–916.

  • Huang Y, Ohtani K, Iwanaga R, Matsumura Y and Nakamura M . (2001). Oncogene, 20, 1094–1102.

  • Hurt EM, Wiestner A, Rosenwald A, Shaffer AL, Campo E, Grogan T, Bergsagel PL, Kuehl WM and Staudt LM . (2004). Cancer Cell, 5, 191–199.

  • Kozar K, Ciemerych MA, Rebel VI, Shigematsu H, Zagozdzon A, Sicinska E, Geng Y, Yu Q, Bhattacharya S, Bronson RT, Akashi K and Sicinski P . (2004). Cell, 118, 477–491.

  • Lavoie JN, L'Allemain G, Brunet A, Muller R and Pouyssegur J . (1996). J. Biol. Chem., 271, 20608–20616.

  • Lee RJ, Albanese C, Fu M, D'Amico M, Lin B, Watanabe G, Haines Gkr, Siegel PM, Hung MC, Yarden Y, Horowitz JM, Muller WJ and Pestell RG . 2000. Mol. Cell. Biol., 20, 672–683.

  • Lee RJ, Albanese C, Stenger RJ, Watanabe G, Inghirami G, Haines III GK, Webster M, Muller WJ, Brugge JS, Davis RJ and Pestell RG . (1999). J. Biol. Chem., 274, 7341–7350.

  • Liu JJ, Chao JR, Jiang MC, Ng SY, Yen JJ and Yang-Yen HF . (1995). Mol. Cell. Biol., 15, 3654–3663.

  • Malstrom S, Tili E, Kappes D, Ceci JD and Tsichlis PN . (2001). Proc. Natl. Acad. Sci. USA, 98, 14967–14972.

  • Marshall C . (1999). Curr. Opin. Cell Biol., 11, 732–736.

  • Muise-Helmericks RC, Grimes HL, Bellacosa A, Malstrom SE, Tsichlis PN and Rosen N . (1998). J. Biol. Chem., 273, 29864–29872.

  • Perez-Roger I, Kim SH, Griffiths B, Sewing A and Land H . (1999). EMBO J., 18, p5310–p5320.

  • Sherr CJ and Roberts JM . (1999). Genes Dev., 13, p1501–p1512.

  • Shtutman M, Zhurinsky J, Simcha I, Albanese C, D'Amico M, Pestell R and Ben-Ze'ev A . (1999). Proc. Natl. Acad. Sci. USA, 96, 5522–5527.

  • Sicinska E, Aifantis I, Le Cam L, Swat W, Borowski C, Yu Q, Ferrando AA, Levin SD, Geng Y, von Boehmer H and Sicinski P . (2003). Cancer Cell, 4, 451–461.

  • Sicinski P, Donaher JL, Geng Y, Parker SB, Gardner H, Park MY, Robker RL, Richards JS, McGinnis LK, Biggers JD, Eppig JJ, Bronson RT, Elledge SJ and Weinberg RA . (1996). Nature, 384, 470–474.

  • Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslam SZ, Bronson RT, Elledge SJ and Weinberg RA . (1995). Cell, 82, 621–630.

  • Soh JW and Weinstein IB . (2003). J. Biol. Chem., 278, 34709–34716.

  • Terada Y, Tanaka H, Okado T, Shimamura H, Inoshita S, Kuwahara M and Sasaki S . (2003). J. Am. Soc. Nephrol., 14, 1223–1233.

  • Tetsu O and McCormick F . (1999). Nature, 398, 422–426.

  • Virolle T, Krones-Herzig A, Baron V, De Gregorio G, Adamson ED and Mercola D . (2003). J. Biol. Chem., 278, 11802–11810.

  • Yang M, Nomura H, Hu Y, Kaneko S, Kaneko H, Tanaka M and Nakashima K . (1998). Biochem. Mol. Biol. Int., 44, 51–58.

  • Yu Q, Geng Y and Sicinski P . (2001). Nature, 411, p1017–p1021.

  • Zou X, Ray D, Aziyu A, Christov K, Boiko AD, Gudkov AV and Kiyokawa H . (2002). Genes Dev., 16, 2923–2934.

Download references

Acknowledgements

We thank members of the Sicinski lab for help and advice. This work was supported by grants from the State Committee for Scientific Research (KBN) to MAC (3P04C 002 25) and from the NIH (R01 CA83688) to PS.

Author information

Author notes

  1. Qunyan Yu and Maria A Ciemerych: These two authors contributed equally to this work

Authors and Affiliations

  1. Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, 02115, Massachusetts, USA

    Qunyan Yu, Maria A Ciemerych & Piotr Sicinski

  2. Department of Pathology, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Qunyan Yu, Maria A Ciemerych & Piotr Sicinski

  3. Department of Cell Biology, Beijing Cancer Hospital, Peking University School of Oncology, Beijing, 100034, PR China

    Qunyan Yu

  4. Department of Embryology, Institute of Zoology, University of Warsaw, Warsaw, 02-096, Poland

    Qunyan Yu & Maria A Ciemerych

Authors
  1. Qunyan Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria A Ciemerych
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Piotr Sicinski
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Piotr Sicinski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, Q., Ciemerych, M. & Sicinski, P. Ras and Myc can drive oncogenic cell proliferation through individual D-cyclins. Oncogene 24, 7114–7119 (2005). https://doi.org/10.1038/sj.onc.1208853

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208853

Keywords

This article is cited by

Search

Advanced search

Quick links