Expression of COX-2, NF-kappaB-p65, NF-kappaB-p50 and IKKalpha in malignant and adjacent normal human colorectal tissue

M P Charalambous, T Lightfoot, V Speirs, K Horgan, N J Gooderham

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Abstract

BACKGROUND: Cyclooxygenase-2 (COX-2) is selectively over-expressed in colorectal tumours. The mechanism of COX-2 induction in these tumours is not fully understood, although evidence suggests a possible link between nuclear factor (NF)-kappaB and COX-2. We hypothesised an association between COX-2 expression and NF-kappaB-p65, NF-kappaB-p50 and IkappaB-kinase-alpha (IKKalpha) in both epithelial and stromal cells in human colorectal cancer.

METHODS: Using immunohistochemistry, we measured COX-2, NF-kappaB-p65, NF-kappaB-p65 nuclear localisation sequence (NLS), NF-kappaB-p50, NF-kappaB-p50 NLS and IKKalpha protein expression in matched colorectal biopsy samples comprising both non-tumour and adjacent tumour tissue from 32 patients with colorectal cancer.

RESULTS: We have shown that stromal cells of malignant and surrounding normal colorectal tissue express COX-2. In all cell types of malignant tissue, and in vascular endothelial cells (VECs) of neighbouring normal tissue, COX-2 expression was strongly associated with NF-kappaB-p65 expression (Pearson's correlation, P=0.019 for macrophages, P=0.001 for VECs, P=0.002 for fibroblasts (malignant tissue), and P=0.011 for VECs (non-malignant tissue)) but not NF-kappaB-p50 or IKKalpha.

CONCLUSIONS: These data suggest that in these cells COX-2 induction may be mediated through activation of the canonical NF-kappaB pathway. Finally, the lack of association between COX-2, NF-kappaB-p65 or IKKalpha in stromal cells with the clinical severity of colorectal cancer as determined by Duke's stage, suggests that COX-2, NF-kappaB-p65 and IKKalpha expression are possibly early post-initiation events, which could be involved in tumour progression.

Original languageEnglish
Pages (from-to)106-115
Number of pages10
JournalBritish Journal of Cancer
Volume101
Issue number1
DOIs
Publication statusPublished - 7 Jul 2009

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Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Biopsy
  • Colorectal Neoplasms
  • Cyclooxygenase 2
  • Female
  • Humans
  • I-kappa B Kinase
  • Immunohistochemistry
  • Male
  • Middle Aged
  • NF-kappa B p50 Subunit
  • Transcription Factor RelA
  • Journal Article
  • Research Support, Non-U.S. Gov't

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