Tumor metastasis and the reciprocal regulation of heparanase gene expression by nuclear factor kappa B in human gastric carcinoma tissue

Abstract

Aim: To investigate whether NF-κB is activated in human gastric carcinoma tissues and, if so, to study whether there is any correlation between NF-κB activity and heparanase expression in gastric carcinoma. Methods: NF-κB activation was assayed by immunohistochemical staining in formalin-fixed, paraffin-embedded specimens from 45 gastric carcinoma patients. Electrophoretic mobility shift assay (EMSA) method was used for nuclear protein from these fresh tissue specimens. Heparanase gene expression was quantified using quantitative RT-PCR. Results: The nuclear translocation of RelA (marker of NF-κ activation) was significantly higher in tumor cells compared to adjacent and normal epithelial cells [(41.3±3.52)% vs (0.38±0.22) %, t = 10.993, P = 0.000<0.05; (41.3±3.52)% vs (0±0.31)%, t = 11.484, P = 0.000<0.05]. NF-κB activation was correlated with tumor invasion-related clinicopathological features such as lymphatic invasion, pathological stage, and depth of invasion (Z = 2.148, P = 0.032<0.05; χ2 = 8.758, P = 0.033<0.05; χ2 = 18.531, P = 0.006<0.05). NF-κB activation was significantly correlated with expression of heparanase gene (r= 0.194, P= 0.046<0.05). Conclusion: NF-κB RelA (p65) activation was related with increased heparanase gene expression and correlated with poor clinicopathological characteristics in gastric cancers. This suggests NF-κB as a major controller of the metastatic phenotype through its reciprocal regulation of some metastasis-related genes. © 2005 The WJG Press and Elsevier Inc. All rights reserved.