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

Research output: Contribution to journalArticle

54 Citations (Scopus)
3 Downloads (Pure)

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

Fingerprint

I-kappa B Kinase
Cyclooxygenase 2
Colorectal Neoplasms
Stromal Cells
Endothelial Cells
eIF-2 Kinase
Neoplasms
Fibroblasts

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

Cite this

Expression of COX-2, NF-kappaB-p65, NF-kappaB-p50 and IKKalpha in malignant and adjacent normal human colorectal tissue. / Charalambous, M P; Lightfoot, T; Speirs, V; Horgan, K; Gooderham, N J.

In: British Journal of Cancer, Vol. 101, No. 1, 07.07.2009, p. 106-115.

Research output: Contribution to journalArticle

Charalambous, M P ; Lightfoot, T ; Speirs, V ; Horgan, K ; Gooderham, N J. / Expression of COX-2, NF-kappaB-p65, NF-kappaB-p50 and IKKalpha in malignant and adjacent normal human colorectal tissue. In: British Journal of Cancer. 2009 ; Vol. 101, No. 1. pp. 106-115.
@article{e12f78e794e54df9be8254814c5be84f,
title = "Expression of COX-2, NF-kappaB-p65, NF-kappaB-p50 and IKKalpha in malignant and adjacent normal human colorectal tissue",
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.",
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",
author = "Charalambous, {M P} and T Lightfoot and V Speirs and K Horgan and Gooderham, {N J}",
year = "2009",
month = "7",
day = "7",
doi = "10.1038/sj.bjc.6605120",
language = "English",
volume = "101",
pages = "106--115",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Expression of COX-2, NF-kappaB-p65, NF-kappaB-p50 and IKKalpha in malignant and adjacent normal human colorectal tissue

AU - Charalambous, M P

AU - Lightfoot, T

AU - Speirs, V

AU - Horgan, K

AU - Gooderham, N J

PY - 2009/7/7

Y1 - 2009/7/7

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Biopsy

KW - Colorectal Neoplasms

KW - Cyclooxygenase 2

KW - Female

KW - Humans

KW - I-kappa B Kinase

KW - Immunohistochemistry

KW - Male

KW - Middle Aged

KW - NF-kappa B p50 Subunit

KW - Transcription Factor RelA

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/sj.bjc.6605120

DO - 10.1038/sj.bjc.6605120

M3 - Article

VL - 101

SP - 106

EP - 115

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 1

ER -