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Transformation by the simian virus 40 T antigen is regulated by IGF-I receptor and IRS-1 signaling

Oncogene volume 25, pages 32–42 (2006)Cite this article

Abstract

Previous work has shown that the Simian Virus 40 T antigen (T antigen) cannot transform mouse embryo fibroblasts (MEFs) that do not express the type 1 insulin-like growth factor receptor (IGF-IR). We have now investigated the mechanism(s) by which the transforming activity of T antigen is affected by IGF-IR signaling. We demonstrate that transformation by T antigen of MEFs and several other cell lines requires an insulin receptor substrate-1 (IRS-1) phosphorylated on tyrosines. If IRS-1 is not expressed, or is serine phosphorylated or otherwise inactive, T antigen fails to transform cells in culture. For instance, while T antigen cannot transform 32D myeloid cells (that do not express IRS-1), its transforming activity is restored by the expression of a wild-type IRS-1, but not of an IRS-1 mutated at the PI3K binding sites. The importance of IRS-1 activation of PI3K in T-antigen transformation is supported by the finding that a constitutively activated p110 subunit of PI3K, a target of IRS-1, overcomes the inability of T antigen to transform MEFs with a serine phosphorylated IRS-1. Taken together, these results indicate that the IRS-1/PI3K signaling is one of the mechanisms regulating transformation by the SV40 T antigen. We propose that the requirement for a tyrosyl-phosphorylated IRS-1 provides a mechanism to explain the failure of T antigen to transform MEFs with deleted IGF-IR genes.

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References

  • Ali SH, DeCaprio JA . (2001). Semin Cancer Biol 11: 15–22.

  • Baserga R . (2000). Oncogene 19: 5574–5581.

  • Baserga R . (2004). In: Cell Growth: Control of Cell Size. Hall MN, Raff M and Thomas G (eds). Cold Spring Harbor Laboratory Press: Cold Spring Harbor, pp. 235–263.

    Google Scholar 

  • Belletti B, Prisco M, Morrione A, Valentinis B, Navarro M, Baserga R . (2001). J Biol Chem 276: 13867–13874.

  • Castles GC, Fuqua SA, Klotz DM, Hill SM . (1993). Cancer Res 53: 5934–5939.

  • D'Ambrosio C, Keller SR, Morrione A, Lienhard GE, Baserga R, Surmacz E . (1995). Cell Growth Diff 6: 557–562.

  • Del Valle L, Wang JY, Lassak A, Peruzzi F, Croul S, Khalili K et al. (2002). J Neuro Virol 8: 138–147.

  • Dickson RB, Lippman ME . (1995). Endocrine Rev 16: 559–589.

  • Drakas R, Tu X, Baserga R . (2004). Proc Natl Acad Sci 101: 9272–9276.

  • Eves EM, Tucker MS, Roback JD, Downen M, Rosner MR, Wainer BH . (1992). Proc Natl Acad Sci 89: 4373–4377.

  • Fanning E . (1992). J Virol 66: 1289–1293.

  • Grummt I . (1999). Prog Nucl Acid Res Mol Biol 62: 109–153.

  • Hermanto U, Zong CS, Wang LH . (2000). Cell Growth Diff 11: 655–664.

  • Klippel A, Escobedo MA, Wachowicz MS, Apell G, Brown TW, Giedlin MA et al. (1998). Mol Cell Biol 18: 5699–5711.

  • Lassak A, DelValle L, Peruzzi F, Wang JY, Enam S, Croul S et al. (2002). J Biol Chem 277: 17231–17238.

  • Lieberman I, Abrams R, Ove P . (1963). J Biol Chem 238: 2141–2149.

  • Liu J-P, Baker J, Perkins AS, Robertson EJ, Efstratiadis A . (1993). Cell 75: 59–72.

  • Liu JL, Blakesley VA, Gutkind JS, LeRoith D . (1997). J Biol Chem 272: 29438–29441.

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

  • Morrione A, Valentinis B, Xu SQ, Yumet G, Louvi A, Efstratiadis A et al. (1997). Proc Natl Acad Sci USA 94: 3777–3782.

  • Morrione A, Romano G, Navarro M, Reiss K, Valentinis B, Dews M et al. (2000). Cancer Res 60: 2263–2272.

  • Morrione M, Navarro N, Romano G, Dews M, Reiss K, Valentinis B et al. (2001). Oncogene 20: 4842–4852.

  • Myers Jr MG, Grammer TC, Wang LM, Su XJ, Pierce JH, Blenis J et al. (1994). J Biol Chem 269: 28783–28789.

  • Nolan MK, Jankowska L, Prisco M, Xu SQ, Guvakova MA, Surmacz E . (1997). Int J Cancer 72: 828–834.

  • Peruzzi F, Prisco M, Dews M, Salomoni P, Grassilli E, Romano G et al. (1999). Mol Cell Biol 19: 7203–7215.

  • Peterson JE, Jelinek T, Kaleko M, Siddle K, Weber MJ . (1994). J Biol Chem 269: 27315–27321.

  • Pietrzkowski Z, Lammers R, Carpenter G, Soderquist AM, Limardo M, Phillips PD et al. (1992). Cell Growth Diff 3: 199–205.

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

  • Prisco M, Santini F, Baffa R, Liu M, Drakas R, Wu A et al. (2002). J Biol Chem 277: 32078–32085.

  • Prisco M, Romano G, Peruzzi F, Valentinis B, Baserga R . (1999). Horm Metab Res 31: 81–89.

  • Reiss K, Valentinis B, Tu X, Xu SQ, Baserga R . (1998). Exp Cell Res 242: 361–372.

  • Reiss K, Wang JY, Romano G, Tu X, Peruzzi F, Baserga R . (2001). Oncogene 20: 490–500.

  • Rubini M, Hongo A, D'Ambrosio C, Baserga R . (1997). Exp Cell Res 230: 284–292.

  • Santos M, Butel J . (1982). J Cell Biochem 19: 127–144.

  • Sciacca L, Costantino A, Pandini G, Mineo R, Frasca F, Scalia P et al. (1999). Oncogene 18: 2471–2479.

  • Sell C, Dumenil G, Deveaud C, Miura M, Coppola D, DeAngelis T et al. (1994). Mol Cell Biol 14: 3604–3612.

  • Sell C, Rubini M, Rubin R, Liu J-P, Efstratiadis A, Baserga R . (1993). Proc Natl Acad Sci USA 90: 11217–11221.

  • Soprano KJ, Dev VG, Croce C, Baserga R . (1979). Proc Natl Acad Sci 76: 3885–3889.

  • Soprano KJ, Galanti N, Jonak GJ, McKercher S, Pipas JM, Peden KWC et al. (1983). Mol Cell Biol 3: 214–219.

  • Sun HZ, Tu X, Prisco M, Wu A, Casiburi I, Baserga R . (2003). Mol Endocrinol 17: 472–486.

  • Sun XJ, Crimmins DL, Myers Jr MG, Miralpeix M, White MF . (1993). Mol Cell Biol 13: 7418–7428.

  • Sun XJ, Pons S, Wang LM, Zhang Y, Yenush L, Burks D et al. (1997). Mol Endocrinol 11: 251–262.

  • Toillon RA, Chopin V, Jouy N, Fauquette W, Boilly B, Le Bourhis X . (2002). Breast Cancer Res Treat 71: 269–280.

  • Tu X, Batta P, Innocent N, Prisco M, Casaburi I, Belletti B et al. (2002). J Biol Chem 277: 44357–44365.

  • Valentinis B, Baserga R . (2001). J Clin Path: Mol Pathol 54: 133–137.

  • Valentinis B, Morrione A, Taylor SJ, Baserga R . (1997). Mol Cell Biol 17: 3744–3754.

  • Valentinis B, Navarro M, Zanocco-Marani T, Edmonds P, McCormick J, Morrione A et al. (2000). J Biol Chem 275: 25451–25459.

  • Valentinis B, Porcu PL, Quinn K, Baserga R . (1994). Oncogene 9: 825–831.

  • Valentinis B, Romano G, Peruzzi F, Morrione A, Prisco M, Soddu S et al. (1999). J Biol Chem 274: 12423–12430.

  • Voit R, Kuhn A, Sander EE, Grummt I . (1995). Nucl Acids Res 23: 2593–2599.

  • Voit R, Schnapp A, Kuhn A, Rosenbauer H, Hirschmann P, Stunnenberg HG et al. (1992). EMBO J 11: 221–228.

  • Wang LM, Myers Jr MG, Sun XJ, Aaronson SA, White M, Pierce JH . (1993). Science 261: 1591–1594.

  • White MF . (1998). Mol Cell Biochem 182: 3–11.

  • White RJ . (2004). In: Cell Growth: Control of Cell Size. Hall MN, Raff M and Thomas G (eds). Cold Spring Harbor Laboratory Press: Cold Spring Harbor, pp. 371–412.

    Google Scholar 

  • Wu A, Sciacca L, Baserga R . (2003). J Cell Physiol 195: 453–460.

  • Yenush L, Fernandez R, Myers Jr MG, Grammer TC, Sun XJ, Blenis J et al. (1996). Mol Cell Biol 16: 2509–2517.

  • Yenush L, Zanella C, Uchida T, Bernal D, White MF . (1998). Mol Cell Biol 18: 6784–6794.

  • Zamorano J, Wang HY, Wang L-M, Pierce JH, Keegan AD . (1996). J Immunol 157: 4926–4934.

  • Zhai W, Tuan J, Comai L . (1997). Genes Dev 11: 1605–1617.

  • Zhou-Li F, D'Ambrosio C, Li S, Surmacz E, Baserga R . (1995). Mol Cell Biol 15: 4232–4239.

  • Zhou-Li F, Xu S-Q, Dews M, Baserga R . (1997). Oncogene 15: 961–970.

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Acknowledgements

This work was supported by Grants CA89640 and AG 20956 from the National Institutes of Health.

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  1. Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA

    T DeAngelis, J Chen, A Wu, M Prisco & R Baserga

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  1. T DeAngelis
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  2. J Chen
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  3. A Wu
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  4. M Prisco
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  5. R Baserga
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Correspondence to R Baserga.

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DeAngelis, T., Chen, J., Wu, A. et al. Transformation by the simian virus 40 T antigen is regulated by IGF-I receptor and IRS-1 signaling. Oncogene 25, 32–42 (2006). https://doi.org/10.1038/sj.onc.1209013

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