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The SV40 small t-antigen prevents mammary gland differentiation and induces breast cancer formation in transgenic mice; truncated large T-antigen molecules harboring the intact p53 and pRb binding region do not have this effect

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Abstract

We report here for the first time, that the SV40 small t-antigen inhibits mammary gland differentiation during mid-pregnancy and that about 10% of multiparous WAP-SVt transgenic animals develop breast tumors with latencies ranging from 10–17 months. Cyclin D1 is deregulated and over expressed in the small t-antigen positive mammary gland epithelial cells (ME-cells) and in the breast tumor cells. SV40 small t-antigen immortalized ME-cells (t-ME-cells) exhibit a strong intranuclear cyclin D1 staining, also in the absence of external growth factors and the cells continue to divide for several days without serum. In addition, the expression rate of cyclin E and p21Waf1 but not of p53 is increased. Coimmunoprecipitation experiments revealed that p21Waf1 is mainly associated with the cyclin D/CDK4 but not with the cyclin E/CDK2 complex. WAP-SVT transgenic animals exhibit an almost regular mammary gland development until late pregnancy but the majority of the ME-cells are eliminated by apoptosis during the early lactation period. Tumor formation is delayed and less efficient than in T/t-antigen positive animals. Sequestration of p53 and pRb by the N-terminal truncated T-antigen molecules (T1-antigen and T2-antigen) does not affect mammary gland differentiation and the transgenic animals (WAP-SVBst-Bam) do not develop breast tumors.

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References

  • Cicala C, Avantaggiati ML, Graessmann A, Rundell K, Levine AS, Carbone M . 1994 J. Virol. 68: 3138–3144

  • DeCaprio JA . 1999 Biologicals 27: 23–28

  • Dotto GP . 2000 Biochem. Biophys. Acta 1471: M43–M56

  • Eul J, Graessmann M, Graessmann A . 1995 EMBO J. 14: 3226–3235

  • Garcia A, Cereghinie S, Sontag E . 2000 J. Biol. Chem. 31: 9385–9389

  • Hunter T, Pines J . 1994 Cell 79: 573–582

  • Kohlhoff S, Ziechmann C, Gottlob K, Graessmann M . 2000 Free Rad. Biol. Med. 29: 497–506

  • Li M, Lewis B, Capuco AV, Laucirica R, Furth PA . 2000 Oncogene 19: 1010–1019

  • Martin RG, Setlour VP, Edwards CA . 1979 J. Virol. 31: 596–607

  • May P, May E . 1999 Oncogene 18: 7621–7636

  • Mumby MC, Walter G . 1991 Cell regulation 2: 589–598

  • Mumby MC, Walter G . 1993 Physiol. Rev. 73: 673–699

  • Rundell K . 1987 J. Virol. 61: 1240–1243

  • Santarelli R, Tzeng YJ, Zimmermann C, Guhl E, Graessmann A . 1996 Oncogene 12: 495–505

  • Scheidtmann KH, Echle B, Walter G . 1982 J. Virol. 44: 116–133

  • Schulze-Garg C, Löhler J, Gocht A, Deppert W . 2000 Oncogene 19: 1028–1037

  • Senkiti S, Banerjee MR . 1979 Biochem. Biophys. Acta 582: 79–88

  • Siegel PM, Hardy WR, Muller WJ . 2000 BioEssays 22: 554–563

  • Sontag E, Sontag JM, Garcia A . 1997 EMBO J. 16: 5662–5671

  • Tzeng YJ, Guhl E, Graessmann M, Graessmann A . 1993 Oncogene 8: 1965–1971

  • Tzeng YJ, Gottlob K, Santarelli R, Graessmann A . 1996 FEBS Lett. 380: 215–218

  • Tzeng YJ, Zimmermann C, Guhl E, Berg B, Avantaggiati ML, Graessmann A . 1998 Oncogene 16: 2103–2114

  • Virshup DM . 2000 Curr. Opin. Cell Biol. 12: 180–185

  • Wakasugi E, Kobayashi T, Tamaki Y, Ito Y, Miyashiro I, Komoike Y, Takeda T, Shin E, Takatsuka Y, Kikkawa N, Monden T, Monden M . 1997 Am. J. Clin. Pathol. 107: 684–691

  • Wang S, Counterman LJ, Haslam SZ . 1990 Endocrinology 127: 2183–2189

  • Wang TC, Cardiff RD, Zukerberg L, Lees M, Arnold A, Schmidt EV . 1994 Nature 369: 669–671

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Acknowledgements

This work was supported by the Wilhelm Sander-Stiftung (93.005.4) and Verband der Chemischen Industrie.

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Authors and Affiliations

  1. Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Arnimallee 22, Berlin, 14195, Germany

    F Goetz, E Guhl, M Graessmann & A Graessmann

  2. Graduate Institute of Molecular and Cell Biology, Tzu-Chi University, Hualien, 970, Taiwan

    Y J Tzeng

  3. Institut für Anatomie Freie Universität Berlin, Königin-Luise-Str. 15, Berlin, 14195, Germany

    J Merker

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  1. F Goetz
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  2. Y J Tzeng
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  3. E Guhl
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  4. J Merker
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  5. M Graessmann
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  6. A Graessmann
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Goetz, F., Tzeng, Y., Guhl, E. et al. The SV40 small t-antigen prevents mammary gland differentiation and induces breast cancer formation in transgenic mice; truncated large T-antigen molecules harboring the intact p53 and pRb binding region do not have this effect. Oncogene 20, 2325–2332 (2001). https://doi.org/10.1038/sj.onc.1204355

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  • DOI: https://doi.org/10.1038/sj.onc.1204355

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