Nuclear factor-kappa B regulates cyclooxygenase-2 expression and cell proliferation in human colorectal carcinoma tissue.
OBJECTIVE
Activation of transcription factor nuclear factor-kappa B (NF-kappa B) has been shown to play a role in cell proliferation, apoptosis, cytokine production, and oncogenesis. The purpose of this study was to determine whether NF-kappa B is constitutively activated in human colorectal tumor tissues and, if so, to determine the role of NF-kappa B in colorectal tumorigenesis, furthermore, to determine the association of RelA expression with the expression of cyclooxygenase-2 (COX-2) and tumor cell proliferation.


METHODS
Paraffin sections of the normal epithelial, adenomatous and adenocarcinoma tissue were analysed immunohistochemically for RelA, COX-2, Ki-67 protein expression. EMSA (electrophoretic mobility shift assay) was used to confirm the increased nuclear translocation of RelA in colorectal tumor tissues. The expression of COX-2 mRNA was determined by RT-PCR (reverse transcription polymerase chain reaction) analysis.


RESULTS
Activation of NF-kappa B was significantly higher in adenocarcinoma tissue in comparison to that in adenomatous and normal epithelial tissue. The colon tumor cell proliferation, mRNA expression and protein level of COX-2 were significantly increased in the transition from normal to tumor tissue.


CONCLUSIONS
Our results suggest that NF-kappa B may promote proliferation via enhancing the expression of COX-2, and the increased expression of RelA/nuclear factor-kappa B plays an important role in the pathogenesis of colorectal carcinoma.
Yu
Liang-Liang
LL
Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, China. yuliangliang@sina.com
Yu
Hong-Gang
HG
Yu
Jie-Ping
JP
Luo
He-Sheng
HS
D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D007527:Isoenzymes / Q000096:biosynthesis*; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008565:Membrane Proteins; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D016328:NF-kappa B; D051996:Transcription Factor RelA; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases