Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression.

OBJECTIVES Nuclear factor-kB (NF-kB) is a transcription factor that participates in the induction of several genes for cytokines and enzymes that play important functional roles in various cell types. The aim of this study was to determine NF-kB activation status in human colorectal carcinoma and its correlation to the clinicopathological characteristics of patients. MATERIALS AND METHODS We examined the activation status of NF-kB in 28 resected colorectal carcinomas and in colonic mucosa from uninvolved portions of these specimens by electrophoretic mobility shift assay (EMSA) and immunohistochemical staining for the p65 subunit of NF-kB. RESULTS EMSA showed much greater activation in the tumors than in normal mucosa, as did epithelial p65 immunostaining. NF-kB activation significantly increased in the more progressed cases (T3 + T4 cases or Stage II< cases). In vitro studies using lipopolysaccharide (LPS)-responsive colon carcinoma cells suggested a correlation between NF-kB activation and cell proliferation. CONCLUSION Our findings indicated that NF-kB is constitutively activated in human colorectal carcinoma tissue and correlates with tumor progression. The regulation of this transcription factor might be therapeutically useful against these tumors.