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Activation of N-ras and K-ras induced by interleukin-6 in a myeloma cell line: implications for disease progression and therapeutic response

Oncogene volume 21, pages 8769–8775 (2002)Cite this article

Abstract

Ras is a major signaling molecule activated by interleukin-6. There have been no published reports, however, that specifically examine the kinetics and percentage of Ras activation in response to IL-6. Model cell lines were used to study activation of N- and K-ras induced by IL-6. All of the myeloma cell lines we tested express both N-ras and K-ras, but not H-ras. GTP-bound Ras was measured and the percentage of the total Ras pool that was activated in response to IL-6 was calculated. IL-6 is able to transiently activate both N- and K-ras in the ANBL6 cell line. In addition, increasing concentrations of IL-6 are able to activate increasing levels of both N- and K-ras. One ng/ml of IL-6 is able to activate approximately 10% of the N-ras pool and 18% of the K-ras pool. The amount of Ras-GTP in the cells correlates with the level of proliferation at low levels, but proliferation plateaus when higher levels of Ras-GTP are present. Protection from dexamethasone-induced apoptosis correlates with IL-6 concentration and Ras activation. However, IL-6 enhances apoptosis induced by doxorubicin. Interestingly, the ANBL6 cell line transfected with an N-ras12 or a K-ras12 gene is protected from doxorubicin-induced apoptosis.

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References

  • Bataille R, Jourdan M, Zhang XG, Klein B . 1989 J. Clin. Invest. 84: 2008–2011

  • Billadeau D, Jelinek DF, Shah N, LeBien TW, Van Ness B . 1995 Cancer Res. 55: 3640–3646

  • Billadeau D, Liu P, Jelinek D, Shah N, LeBien TW, Van Ness B . 1997 Cancer Res. 57: 2268–2275

  • Brownell HL, Firth KL, Kawauchi K, Delovitch T, Raptis L . 1997 DNA Cell. Biol. 16: 103–110

  • Chauhan D, Pandey P, Ogata A, Teoh G, Krett N, Halgren R, Rosen S, Kufe D, Kharbanda S, Anderson K . 1997a J. Biol. Chem. 272: 29995–29997

  • Chauhan D, Pandey P, Ogata A, Teoh G, Treon S, Urashima M, Kharbanda S, Anderson KC . 1997b Oncogene 15: 837–843

  • Corradini P, Ladetto M, Voena C, Palumbo A, Inghirami G, Knowles DM, Boccadoro M, Pileri A . 1993 EMBO J. 16: 6439–6451

  • Hall A . 1998 Science 280: 2074–2075

  • Hardin J, MacLeod S, Grigorieva I, Chang R, Barlogie B, Xiao H, Epstein J . 1994 Blood 84: 3063–3070

  • Hata Y, Natsumeda Y, Weber G . 1993 Oncol. Res. 5: 161–164

  • Hirano T, Nakajima K, Hibi M . 1997 Cytokine Growth Factor Rev. 8: 241–252

  • Jones MK, Jackson JH . 1998 J. Biol. Chem. 273: 1782–1787

  • Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A, Kishimoto T . 1988 Nature 332: 83–85

  • Klein B, Zhang XG, Jourdan M, Content J, Houssiau F, Aarden L, Piechaczyk M, Bataille R . 1989 Blood 73: 517–526

  • Lichtenstein A, Tu Y, Fady C, Vescio R, Berenson J . 1995 Cell. Immunol. 162: 248–255

  • Liu P, Leong T, Quam L, Billadeau D, Kay NE, Greipp P, Kyle RA, Oken MM, Van Ness B . 1996 Blood 88: 2699–2706

  • McCloskey TW, Oyaizu N, Coronesi M, Pahwa S . 1994 Clin. Immunol. Immunopathol. 71: 14–18

  • McCormick F . 1996 Nat. Struct. Biol. 3: 653–655

  • Nakafuku M, Satoh T, Kaziro Y . 1992 J. Biol. Chem. 267: 19448–19454

  • Neri A, Murphy JP, Cro L, Ferrero D, Tarella C, Baldini L, Dalla-Favera R . 1989 J. Exp. Med. 170: 1715–1725

  • Paquette RL, Berenson J, Lichtenstein A, McCormick F, Koeffler HP . 1990 Oncogene 5: 1659–1663

  • Portier M, Moles JP, Mazars GR, Jeanteur P, Bataille R, Klein B, Theillet C . 1992 Oncogene 7: 2539–2543

  • Rowley M, Liu P, Van Ness B . 2000 Blood 96: 3175–3180

  • Takai Y, Sasaki T, Matozaki T . 2001 Physiol. Rev. 81: 153–208

  • Taylor SJ, Shalloway D . 1996 Curr. Biol. 6: 1621–1627

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Acknowledgements

We wish to thank Richard Roof and the Daniel Mueller lab for reagents and technical support for the activated Ras interaction assay. This work was supported by the National Institutes of Health grant P01CA62242.

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  1. Graduate Program in Molecular, Cellular, Developmental Biology and Genetics, The University of Minnesota, Minneapolis, 55455, Minnesota, MN, USA

    Matt Rowley

  2. The Department of Genetics, Cell Biology and Development, The University of Minnesota, Minneapolis, 55455, Minnesota, MN, USA

    Brian Van Ness

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Correspondence to Brian Van Ness.

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Rowley, M., Van Ness, B. Activation of N-ras and K-ras induced by interleukin-6 in a myeloma cell line: implications for disease progression and therapeutic response. Oncogene 21, 8769–8775 (2002). https://doi.org/10.1038/sj.onc.1205387

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