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

James C H Hardwick, Gijs R. Van Den Brink, G. J. Offerhaus, Sander J H Van Deventer, Maikel P. Peppelenbosch

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)819-827
Number of pages9
JournalOncogene
Volume20
Issue number7
DOIs
StatePublished - Feb 15 2001
Externally publishedYes

Keywords

  • COX-2
  • JNK
  • NF-kappaB
  • NSAIDs
  • p38 MAPK
  • Polyp

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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  • Cite this

    Hardwick, J. C. H., Van Den Brink, G. R., Offerhaus, G. J., Van Deventer, S. J. H., & Peppelenbosch, M. P. (2001). NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps. Oncogene, 20(7), 819-827. https://doi.org/10.1038/sj.onc.1204162