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:

NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps

Oncogene volume 20, pages 819–827 (2001)Cite this article

Abstract

The factors that govern the progression from colonic adenomatous polyp to colon cancer are poorly understood. The observation that NSAIDs act as chemopreventative agents and reduce the size of colonic polyps suggests the involvement of inflammatory signalling, but inflammatory signalling in colonic polyps has not been studied. We investigated the expression of the active forms of NF-κB, JNK and p38 MAPK using immunohistochemistry with activation specific antibodies in human colonic adenomas. We show that active NF-κB is seen in stromal macrophages that also express COX-2 and TNF-α, active JNK is seen in stromal and intraepithelial T-lymphocytes and periendothelial cells of new blood vessels, and active p38 MAPK is most highly expressed in macrophages and other stromal cells. These results demonstrate the presence of active inflammatory signal transduction in colonic polyps and that these are predominantly in the stroma. In the case of NF-κB this coincides with the cellular localisation of COX-2. These results support evidence that NSAIDs may act through effects on stromal cells rather than epithelial cells.

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 5

Similar content being viewed by others

References

  • Bak AW, McKnight W, Li P, Del Soldato P, Calignano A, Cirino G and Wallace JL. . 1998 Life Sci. 62: L367–L373.

  • Bamba H, Ota S, Kato A, Adachi A, Itoyama S and Matsuzaki F. . 1999 Int. J. Cancer 83: 470–475.

  • Chan ED, Winston BW, Jarpe MB, Wynes MW and Riches DW. . 1997 Proc. Natl Acad. Sci. USA 94: 13169–13174.

  • Chapple KS, Cartwright EJ, Hawcroft G, Tisbury A, Bonifer C, Scott N, Windsor AC, Guillou PJ, Markham AF, Coletta PL and Hull MA. . 2000 Am. J. Pathol. 156: 545–553.

  • Charalambous D and O'Brien PE. . 1996 J. Gastroenterol. Hepatol. 11: 307–310.

  • Chen KD, Chen LY, Huang HL, Lieu CH, Chang YN, Chang MD and Lai YK. . 1998 J. Biol. Chem. 273: 749–755.

  • Chiu CH, McEntee MF and Whelan J. . 1997 Cancer Res. 57: 4267–4273.

  • Di Giorgio A, Botti C, Tocchi A, Mingazzini P and Flammia M. . 1992 Int. Surg. 77: 256–260.

  • Gaweco AS, Wiesner RH, Porayko M, Rustgi VK, Yong S, Hamdani R, Harig J, Chejfec G, McClatchey KD and Van Thiel DH. . 2000 Hepatology 31: 1183–1191.

  • Hakansson L, Adell G, Boeryd B, Sjogren F and Sjodahl R. . 1997 Br. J. Cancer 75: 374–380.

  • Hanif R, Pittas A, Feng Y, Koutsos MI, Qiao L, Staiano-Coico L, Shiff SI and Rigas B. . 1996 Biochem. Pharmacol. 52: 237–245.

  • Hong WK and Sporn MB. . 1997 Science 278: 1073–1077.

  • Hull MA, Booth JK, Tisbury A, Scott N, Bonifer C, Markham AF and Coletta PL. . 1999 Br. J. Cancer 79: 1399–1405.

  • Ip YT and Davis RJ. . 1998 Curr. Opin. Cell. Biol. 10: 205–219.

  • Janne PA and Mayer RJ. . 2000 N. Engl. J. Med. 342: 1960–1968.

  • Karin M, Liu Z and Zandi E. . 1997 Curr. Opin. Cell. Biol. 9: 240–246.

  • Kopp E and Ghosh S. . 1994 Science 265: 956–959.

  • Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C, Duhamel O, Trousset M and Attali P. . 1991 Gastroenterology 101: 635–639.

  • Licato LL and Brenner DA. . 1998 Dig. Dis. Sci. 43: 1454–1464.

  • Licato LL, Keku TO, Wurzelmann JI, Murray SC, Woosley JT, Sandler RS and Brenner DA. . 1997 Gastroenterology 113: 1589–1598.

  • Mercurio F and Manning AM. . 1999 Oncogene 18: 6163–6171.

  • Omori S, Hida M, Ishikura K, Kuramochi S and Awazu M. . 2000 Kidney Int. 58: 27–37.

  • Ono K and Han J. . 2000 Cell Signal 12: 1–13.

  • Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF and Taketo MM. . 1996 Cell 87: 803–809.

  • Piazza GA, Rahm AK, Finn TS, Fryer BH, Li H, Stoumen AL, Pamukcu R and Ahnen DJ. . 1997 Cancer Res. 57: 2452–2459.

  • Pirvola U, Xing-Qun L, Virkkala J, Saarma M, Murakata C, Camoratto AM, Walton KM and Ylikoski J. . 2000 J. Neurosci. 20: 43–50.

  • Plummer SM, Holloway KA, Manson MM, Munks RJ, Kaptein A, Farrow S and Howells L. . 1999 Oncogene 18: 6013–6020.

  • Rogler G, Brand K, Vogl D, Page S, Hofmeister R, Andus T, Knuechel R, Baeuerle PA, Scholmerich J and Gross V. . 1998 Gastroenterology 115: 357–369.

  • Sano H, Kawahito Y, Wilder RL, Hashiramoto A, Mukai S, Asai K, Kimura S, Kato H, Kondo M and Hla T. . 1995 Cancer Res. 55: 3785–3789.

  • Schulze-Osthoff K, Ferrari D, Riehemann K and Wesselborg S. . 1997 Immunobiology 198: 35–49.

  • Schwenger P, Alpert D, Skolnik EY and Vilcek J. . 1998 Mol. Cell. Biol. 18: 78–84.

  • Schwenger P, Alpert D, Skolnik EY and Vilcek J. . 1999 J. Cell. Physiol. 179: 109–114.

  • Schwenger P, Bellosta P, Vietor I, Basilico C, Skolnik EY and Vilcek J. . 1997 Proc. Natl. Acad. Sci. USA 94: 2869–2873.

  • Smith K, Bui TD, Poulsom R, Kaklamanis L, Williams G and Harris AL. . 1999 Br. J. Cancer 81: 496–502.

  • Svennevig JL, Lunde OC, Holter J and Bjorgsvik D. . 1984 Br. J. Cancer 49: 375–377.

  • Thun MJ, Namboodiri MM and Heath Jr. CW. . 1991 New Engl. J. Med. 325: 1593–1596.

  • Tsujii M and DuBois RN. . 1995 Cell 83: 493–501.

  • Tsujii M, Kawano S and DuBois RN. . 1997 Proc. Natl. Acad. Sci. USA 94: 3336–3340.

  • Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M and DuBois RN. . 1998 Cell 93: 705–716.

  • van Den Brink GR, ten Kate FJ, Ponsioen CY, Rive MM, Tytgat GN, van Deventer SJ and Peppelenbosch MP. . 2000 J. Immunol. 164: 3353–3359.

  • Williams CS, Tsujii M, Reese J, Dey SK and DuBois RN. . 2000 J. Clin. Invest. 105: 1589–1594.

  • Yamamoto Y, Yin MJ, Lin KM and Gaynor RB. . 1999 J. Biol. Chem. 274: 27307–27314.

  • Yin MJ, Yamamoto Y and Gaynor RB. . 1998 Nature 396: 77–80.

  • Zhang X, Morham SG, Langenbach R and Young DA. . 1999 J. Exp. Med. 190: 451–459.

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands

    James CH Hardwick, Gijs R van den Brink, Sander JH van Deventer & Maikel P Peppelenbosch

  2. Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands

    G J Offerhaus

Authors
  1. James CH Hardwick
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gijs R van den Brink
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G J Offerhaus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sander JH van Deventer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maikel P Peppelenbosch
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hardwick, J., van den Brink, G., Offerhaus, G. et al. NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps. Oncogene 20, 819–827 (2001). https://doi.org/10.1038/sj.onc.1204162

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204162

Keywords

This article is cited by

Search

Advanced search

Quick links