NF-κB and apoptosis in colorectal tumourigenesis

M. M. Aranha, P. M. Borralho, P. Ravasco, I. B. Moreira da Silva, L. Correia, A. Fernandes, M. E. Camilo, C. M. P. Rodrigues*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Background: Nuclear factor-κB (NF-κB) may play an important role in colorectal tumourigenesis, controlling cell cycle and apoptosis gene expression. In addition, imbalances between cell proliferation and cell death are thought to underlie neoplastic development. The aims of this study were to investigate apoptosis and expression of several apoptosis-related proteins, and to determine correlations with colorectal tumour progression. Materials and methods: Apoptosis was evaluated by the TUNEL assay in 48 patient samples, including adenomas, adenocarcinomas and adjacent normal mucosas. Immunohistochemistry was performed for Bcl-2 and NF-κB. Expression levels of p53, Bax and IκB proteins were determined by immunoblotting. Cultured human colon cancer cells were used to evaluate NF-κB expression and nuclear translocation by immunocytochemistry and immunoblotting. Results: Apoptosis and NF-κB immunoreactivity were significantly higher in tumour tissue compared with normal mucosa (P < 0.01), increasing in association with histological tumour progression (P < 0.01). Bcl-2 was consistently higher in normal mucosa (P < 0.01) and inversely correlated with the percentage of apoptosis (P < 0.01). Phosphorylated p53 and Bax levels were similar in tumour tissue and normal mucosa; however, the NF-κB inhibitor, IκB, tended to decrease in tumours. In vitro, nuclear translocation of NF-κB was greater in proliferative than in resting phases of colon cancer cells. Conclusions: NF-κB expression and apoptosis are increased from adenoma to poorly differentiated adenocarcinoma tissues. Apoptosis is correlated with suppression of Bcl-2 expression, but appears to proceed through a p53- and Bax-independent pathway. Activation of NF-κB may play an important role in colorectal tumour progression.
Original languageEnglish
Pages (from-to)416-424
Number of pages9
JournalEuropean Journal of Clinical Investigation
Volume37
Issue number5
DOIs
Publication statusPublished - May 2007
Externally publishedYes

Keywords

  • Apoptosis
  • Bax
  • Bcl-2
  • Colorectal tumours
  • NF-κB
  • p53

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