The ubiquitin-proteasome pathway and enhanced activity of NF-kappaB in gastric carcinoma.
OBJECTIVE
NF-kappa B, ubiquitin and proteasome have been shown be important factors in oncogenesis. The aim of this study was to determine whether NF-kappa B could be a sensitive biomarker for gastric carcinoma.


METHODS
Tumor and adjacent mucosal tissue specimens in 92 patients with gastric carcinoma were studied. The expression of NF-kappa B was evaluated by immunohistochemistry. The expression of I kappa B alpha, ubiquitin in cytoplasm and NF-kappa B in nucleoplasm was assayed by Western blot. DNA binding-activity of NF-kappa B was confirmed by electrophoretic mobility shift assay (EMSA). Fluorogenic technique was performed to measure the 26S proteasome activity.


RESULTS
NF-kappa B positive expression in tumor tissues (82.4%) was significant higher than that in adjacent mucosal tissues (32.7%, P < 0.05). The increase of NF-kappa B activation was accompanied by the increases of ubiqutin, 26S proteasome activation and a degradation of I kappa B alpha but not the ubiquitin-conjugated I kappa B alpha/NF-kappa B complex in gastric carcinoma. NF-kappa B expression was significantly increased in patients with lymph node metastasis, TNM stage III/IV or with the habit of high intake of pickled vegetables.


CONCLUSIONS
This study demonstrates that the constitutive activation of NF-kappa B is likely due to the activation of ubiquitin-proteasome pathway and NF-kappa B can be used as a prognostic biomarker.
Wu
Lingfei
L
Department of Gastroenterology, The Second Affiliated Hospital of Shantou University Medical College, Guangdong, China.
Pu
Zejin
Z
Feng
Jialin
J
Li
Guoping
G
Zheng
Zhichao
Z
Shen
Wenlv
W
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004032:Diet; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism*
D014408:Biomarkers, Tumor; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D025801:Ubiquitin; D000072000:NF-KappaB Inhibitor alpha; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease