Expression of nuclear factor κB in human gastric carcinoma: relationship with IκBa and prognostic significance

Abstract

Nuclear factor (NF)-kappaB is a transcription factor constitutively activated in various neoplasms, including gastric carcinoma. However, its clinical significance in the latter remains an unresolved issue, as published information is limited and controversial. Furthermore, no data is available about the interaction of NF kappaB with its inhibitory protein I kappaB a in gastric carcinoma cases. In this study, the expression of NF kappaB 1/p50 and p I kappaB a protein was evaluated immunohistochemically in paraffin-embedded tissues from 93 patients. The effect of NF kappaB 1/p50 and p I kappaB a on clinical outcome was assessed. Positive immunostaining was detected for nuclear NF kappaB 1/p50, cytoplasmic NF kappa B1/p50 and p I kappaB a in 91, 68 and 85.7% of cases, respectively. A positive correlation emerged between nuclear NF kappa B 1/p50 and p I kappaB a (p < 0.0001) and a negative one between cytoplasmic NF kappaB 1/p50 and p I kappaB a (p = 0.0033). Nuclear NF kappaB 1/p50 was associated with stage (p = 0.0388), the depth of invasion (p = 0.0382), World Health Organization (WHO; p = 0.0326) and Lauren's histological classification (p = 0.0046). NF kappaB 1/p50 nuclear expression adversely affected survival in both univariate and multivariate analysis (p < 0.0001 and p = 0.02, respectively). Our results suggest that NF kappaB 1/p50 nuclear expression and therefore activation is regulated by its interaction with I kappaB a and that the former may serve as a useful independent molecular marker for stratifying patients with gastric carcinoma in terms of prognosis.

Paeoniflorin modulates multidrug resistance of a human gastric cancer cell line via the inhibition of NF-κB activation

“…Emerging evidence suggests that constitutive activation of NF-κB has been observed and positively related to tumor progression in human gastric, and numerous other types of cancer (24)(25)(26). It has also been reported that NF-κB levels are significantly associated with poor prognosis of gastric cancer (27). Guo et al revealed that the activation of the NF-κB dimer was significantly higher in drug-resistant gastric cancer cell lines than its parental cell lines (28).…”

The ubiquitin‐proteasome pathway and enhanced activity of NF‐κB in gastric carcinoma

“…Some studies showed constitutive NF-kB activity depended on the aberrant activation of IKKs and a faster IkBa turnover in prostate carcinoma cell lines [28,29], hepatocellular carcinoma tissues [30], and some gastric carcinoma cell lines [31]. Levidou et al [32] reported that the expression of NF-kB (p50) in the nucleus increased with the increase of pIkBa expression in gastric carcinoma tissues. We found more NF-kB translocated into the nucleus while the total IkBa levels decreased in the cytoplasm of gastric carcinoma tissues.…”

“…A double-stranded NF-kB oligonucleotide probe ( P] ATP (3,000Ci/mmol at 10 mCi/ml), unlabeled probe (10 pmol/ml). Ten micrograms of nuclear extraction were incubated for 20 min at room temperature with 32 P labeled probe and 1 mg/ml poly (dI-dC) in binding buffer containing 10 mM Tris-HCl (PH:8.0), 50 mM NaCl, 1 mM EDTA, 1 mM DTT, 10% (v/v) Glycerol. For supershift assay, nuclear extraction was pre-incubated with 1 mg monoclonal mouse anti-p65 for 30 min at room temperature before the complex was analyzed by EMSA.…”

Nuclear factor-κB expression is predictive of overall survival in patients with cutaneous melanoma

“…Numerous studies have demonstrated that NF-κB is activated in a variety of cancer types, including breast, lung, gastric, esophageal, pancreatic, prostate cancer (33)(34)(35)(36)(37)(38) and melanoma (2,8).…”