Tumor metastasis and the reciprocal regulation of heparanase gene expression by nuclear factor kappa B in human gastric carcinoma tissue.
OBJECTIVE
To investigate whether NF-kappaB is activated in human gastric carcinoma tissues and, if so, to study whether there is any correlation between NF-kappaB activity and heparanase expression in gastric carcinoma.


METHODS
NF-kappaB 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-kappaB 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-kappaB 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; chi(2) = 8.758, P = 0.033<0.05; chi(2) = 18.531, P = 0.006<0.05). NF-kappaB activation was significantly correlated with expression of heparanase gene (r = 0.194, P = 0.046<0.05).


CONCLUSIONS
NF-kappaB RelA (p65) activation was related with increased heparanase gene expression and correlated with poor clinicopathological characteristics in gastric cancers. This suggests NF-kappaB as a major controller of the metastatic phenotype through its reciprocal regulation of some metastasis-related genes.
Cao
Hou-Jun
HJ
Center of Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, Zhejiang Province, China.
Fang
Yong
Y
Zhang
Xing
X
Chen
Wen-Jun
WJ
Zhou
Wen-Peng
WP
Wang
Hong
H
Wang
Lin-Bo
LB
Wu
Jin-Min
JM
D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism*; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics / Q000503:physiopathology* / Q000556:secondary*; D051996:Transcription Factor RelA; D000099175:Heparanase
D005966:Glucuronidase; D016328:NF-kappa B; D051996:Transcription Factor RelA; D000099175:Heparanase