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:

Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells

Oncogene volume 20, pages 7658–7667 (2001)Cite this article

A Corrigendum to this article was published on 11 December 2014

Abstract

Here, we show that fibroblast growth factor-2 (FGF-2) induces proliferation of H-510 and H-69 small cell lung cancer (SCLC) cells. However, the optimal response to FGF-2 was obtained at 10-fold lower concentrations in H-510 cells. This correlated with the selective activation of the mitogen-activated protein kinase kinase (MEK) pathway in H-510, but not H-69 cells. Moreover, inhibition of MEK with PD098059 blocked FGF-2-induced proliferation in H-510 cells only. Similarly, ribosomal protein S6 kinase 2 (S6K2), a recently identified homologue of S6K1 was activated by FGF-2 in H-510, but not H-69 cells. This activation was independent of phosphatidylinositol-3 kinase, but was sensitive to inhibition of the MEK pathway. These data suggest that S6K2 is a novel downstream target of MEK. The potency of FGF-2 in H-510 cells might reflect this additional MEK/S6K2 signalling. In contrast to S6K2, S6K1 was activated in both SCLC cell lines. Inhibition of the mammalian target of rapamycin with 10 ng/ml rapamycin blocked S6K1 activation and proliferation of both lines. However, even at 100 ng/ml, rapamycin only partially inhibited S6K2. Strikingly, this correlated with inhibition of MEK signalling. Our data indicate that S6K1, and possibly S6K2, are involved in FGF-2-induced SCLC cell growth, a notion supported by the overexpression and higher baseline activity of both isoforms in SCLC lines, as compared to normal human type-II pneumocytes.

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 7
Figure 5
Figure 6
Figure 8

Similar content being viewed by others

References

  • Alessi DR, Kozlowski MT, Weng QP, Morrice N, Avruch J . 1998 Curr. Biol. 8: 69–81

  • Bailly K, Soulet F, Leroy D, Amalric F, Bouche G . 2000 FASEB J 14: 333–344

  • Belham C, Comb MJ, Avruch J . 2001 Current Biol. 11: 1155–1167

  • Belinsky SA, Devereaux TR, Foley JF, Maronpot RR, Anderson MW . 1992 Cancer Res. 52: 3164–3173

  • Bikfalvi A, Klein S, Pintucci G, Rifkin DB . 1997 Endocr Rev. 18: 26–45

  • Bunn PA, Dienhart DG, Chan D, Puck TT, Tagawa M, Jewett PB, Braunschweiger E . 1990 Proc. Natl. Acad. Sci. USA 87: 2162–2166

  • Carney DN, Gazdar AF, Minna JD . 1980 Cancer Res. 40: 1820–1823

  • Chellaiah AT, McEwan DG, Werner S, Xu J, Orntiz DM . 1994 J. Biol. Chem. 269: 11620–11627

  • Chou MM, Blenis J . 1995 Curr. Opin. Cell. Biol. 7: 806–814

  • Chung J, Kuo CJ, Crabtree GR, Blenis J . 1992 Cell 69: 1227–1236

  • Cordon-Cardo C, Vlodavsky I, Haimovitz-Friedman A, Hicklin D, Fuks Z . 1990 Lab. Investig. 63: 832–840

  • Dufner A, Thomas G . 1999 Exp. Cell. Res. 253: 100–109

  • Ferrari S, Thomas G . 1994 Crit. Rev. Biochem. Mol. Biol. 29: 385–413

  • Fujimoto K, Ichimori Y, Kakizoe T, Okajima E, Sakamoto H, Sugimura T, Terada M . 1991 Biochem. Biophys. Res. Commun. 180: 386–392

  • Gardner AM, Johnson GL . 1996 J. Biol. Chem. 271: 14560–14566

  • Gazdar AF, Carney DN, Guccion JG, Baylin SB . 1981 Small Cell Lung Cancer Greco FA Oldham FK and Bunn PA. (eds) Grune and Statton, Inc., New York pp. 145–175

  • Gout I, Minami T, Hara K, Tsujishita Y, Filonenko V, Waterfield MD, Yonezawa K . 1998 J. Biol. Chem. 273: 30061–30064

  • Hibi H, Takahashi T, Sekido Y, Ueda R, Hida T, Ariyoshi Y, Takagi H, Takahashi T . 1991 Oncogene 6: 2291–2296

  • Kanda S, Hodgkin MN, Woodfield RJ, Wakelam MJO, Thomas G, Claesson-Welsh L . 1997 J. Biol. Chem. 272: 23347–23353

  • Koh H, Jee K, Lee B, Kim J, Yun YH, Kim JW, Choi HS, Chung J . 1999 Oncogene 18: 5115–5119

  • Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I, Schlessinger J . 1997 Cell 89: 693–702

  • Krystal GW, Hines SJ, Organ CP . 1996 Cancer Res. 56: 370–376

  • Lee-Frumen KK, Kuo CJ, Lippincott J, Terada N, Blenis J . 1999 Oncogene 18: 5108–5114

  • Linder C, Linder S, Munck-Wikland W, Strander H . 1998 Anticancer Res. 18: 2063–2068

  • Macaulay VM, Everard MJ, Teale JD, Trott PA, Van-Wyk JJ, Smith IE, Millar JL . 1990 Cancer Res. 50: 2511–2517

  • Mansukhani A, Dell'Era P, Moscatelli D, Kornbluth S, Hanafusa H, Basilico C . 1992 Proc. Natl. Acad. Sci. USA 89: 3305–3309

  • Martin KA, Schlam SS, Romanelli A, Keon KL, Blenis J . 2001 J. Biol. Chem. 276: 7892–7898

  • Miyake A, Konishi M, Martin FH, Hernday NA, Ozaki K, Yamamoto S, Mikami T, Arakawa T, Itoh N . 1998 Biochem. Biophys. Res. Commun. 243: 148–152

  • Mohammadi M, Dikic I, Sorokin A, Burgess WH, Jaye M, Schlessinger J . 1996 Mol. Cell. Biol. 16: 977–989

  • Mohammadi M, Dionne CA, Li W, Li N, Spivak T, Honnegaer AM, Jaye M, Schlessinger J . 1992 Nature 358: 681–684

  • Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M . 1996 J. Biol. Chem. 271: 15292–15297

  • Plotnikov AN, Schlessinger J, Hubbard SR, Mohammadi M . 1999 Cell 98: 641–650

  • Pullen N, Dennis PB, Andjelkovic M, Dufner A, Kozma SC, Hemmings BA, Thomas G . 1998 Science 279: 707–710

  • Risse-Hackl G, Adamkiewicz J, Wimmel A, Schuermann M . 1998 Oncogene 16: 3057–3068

  • Ron D, Reich R, Chedid M, Lengel C, Cohen OE, Chen AM, Neufeld G, Miki T, Tronick SR . 1993 J. Biol. Chem. 268: 5388–5394

  • Seckl MJ, Rozengurt E . 1998 Clinical and Biological Basis of Lung Cancer Prevention. Martinet Y, Hirsch FR, Martinet N, Vignaud J-M and Mulshine JL (eds). Birkhäuser Verlag: Basel pp. 129–142

  • Seckl MJ, Seufferlein T, Rozengurt E . 1994 Cancer Res. 54: 6143–6147

  • Sethi T, Rozengurt E . 1991 Cancer Res. 51: 3621–3623

  • Seufferlein T, Rozengurt E . 1996 Cancer Res. 56: 3895–3897

  • Shi E, Kan M, Xu J, Wang F, Hou J, McKeehan WL . 1993 Mol. Cell. Biol. 13: 3907–3918

  • Shima H, Pende M, Chen Y, Fumagalli S, Thomas G, Kozma SC . 1998 EMBO J. 17: 6649–6659

  • Smyth JF, Fowlie SM, Gregor A, Crompton GK, Busutill A, Leonard RCF, Grant IWB . 1986 Quart. J. Med. 61: 969–976

  • Szebenyi G, Fallon JF . 1999 Int. Rev. Cytol. 185: 45–106

  • Ten Have-Opbroek AAW, Benfield JR, Krieken JHJH, Dijkman JH . 1997 Histol. Histopathol. 12: 319–336

  • Vainikka S, Partanen J, Bellosta P, Coulier F, BNirnbaum D, Basilico C, Jaye M, Alitalo K . 1992 EMBO J. 11: 4273–4280

  • Valovka T, Filonenko V, Velykyi M, Drobot L, Matsuka G, Gout I . 1999 Biopolymers and Cell 15: 1–7

  • Waskiewicz AJ, Johnson JC, Penn B, Mahalingam M, Kimball SR, Cooper JA . 1999 Mol. Cell. Biol. 19: 1871–1880

  • Wennström S, Downward J . 1999 Mol. Cell. Biol. 19: 4279–4288

  • Wennström S, Siegbahn A, Yokote K, Arvidsson A-K, Heldin C-H, Mori S, Claesson-Welsh L . 1994 Oncogene 9: 651–660

  • Werner S, Duan DR, Devries C, Peters KG, Johnson DE, William LT . 1992 Mol. Cell. Biol. 12: 82–88

  • Witherden IR, Tetley TD . 2001 Human Airway Inflammation: Sampling Techniques and Analytical Protocols. Rogers DF and Donnelly LE. (eds) Humana Press Inc: Totowa, N.J

  • Yiangou C, Cox H, Bansal GS, Coope R, Gomm JJ, Barnard R, Walters J, Groome N, Shousha S, Coombes RC, Johnston CL . 1997 Br. J. Cancer 76: 1419–1427

  • Zubilewicz A, Hecquet C, Jeanny JC, Soubrane G, Courtois Y, Mascarelli F . 2001 Oncogene 20: 1403–1413

Download references

Acknowledgements

We would like to thank Drs J Downward and T Seufferlein for critical reading of the manuscript and the Cancer Research Campaign for supporting the work.

Author information

Authors and Affiliations

  1. Division of Medicine, Lung Cancer Biology Group, Hammersmith Campus of Imperial College School of Medicine, London, W12 ONN, UK

    Olivier E Pardo, Alexandre Arcaro, Giovanni Salerno & Michael J Seckl

  2. Lung Cell Biology National Heart & Lung Institute, Imperial College School of Medicine, London, W6 8RF, UK

    Teresa D Tetley

  3. Cell Regulation Laboratory, Ludwig Institute for Cancer Research, Royal Free and University College Medical School, London, W1W 7BS, UK

    Taras Valovka & Ivan Gout

  4. Institute of Molecular Biology and Genetics, Kyiv, Ukraine

    Ivan Gout

Authors
  1. Olivier E Pardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexandre Arcaro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giovanni Salerno
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Teresa D Tetley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Taras Valovka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ivan Gout
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Michael J Seckl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael J Seckl.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pardo, O., Arcaro, A., Salerno, G. et al. Novel cross talk between MEK and S6K2 in FGF-2 induced proliferation of SCLC cells. Oncogene 20, 7658–7667 (2001). https://doi.org/10.1038/sj.onc.1204994

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204994

Keywords

This article is cited by

Search

Advanced search

Quick links