Nuclear factor-kappaB p65 (RelA) transcription factor is constitutively activated in human colorectal carcinoma tissue.
OBJECTIVE
Activation of transcription factor nuclear factor-kappaB (NF-kappaB) 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-kappaB was constitutively activated in human colorectal tumor tissues and, if so, to determine the role of NF-kappaB in colorectal tumorigenesis, and furthermore, to determine the association of RelA expression with tumor cell apoptosis and the expression of Bcl-2 and Bcl-x(L).


METHODS
Paraffin sections of normal epithelial, adenomatous and adenocarcinoma tissues were analysed immunohistochemically for expression of RelA, Bcl-2 and Bcl-x(L) proteins. Electrophoretic mobility shift assay (EMSA) was used to confirm the increased nuclear translocation of RelA in colorectal tumor tissues. The mRNA expressions of Bcl-2 and Bcl-x(L) were determined by reverse transcription polymerase chain reaction (RT-PCR) analysis. Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method.


RESULTS
The activity of NF-kappaB was significantly higher in adenocarcinoma tissue in comparison with that in adenomatous and normal epithelial tissues. The apoptotic index (AI) significantly decreased in the transition from adenoma to adenocarcinoma. Meanwhile, the expressions of Bcl-2 and Bcl-x(L) protein and their mRNAs were significantly higher in adenocarcinoma tissues than that in adenomatous and normal epithelial tissues.


CONCLUSIONS
NF-kappaB may inhibit apoptosis via enhancing the expression of the apoptosis genes Bcl-2 and Bcl-x(L). And the increased expression of RelA/nuclear factor-kappaB plays an important role in the pathogenesis of colorectal carcinoma.
Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, Hubei Province, China. yuliangliang@sina.com
Liang-Liang
LL
Yu
Hong-Gang
HG
Yu
Jie-Ping
JP
Yu
He-Sheng
HS
Luo
Xi-Ming
XM
Xu
Jun-Hua
JH
Li
D000236:Adenoma / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017209:Apoptosis; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D024202:Electrophoretic Mobility Shift Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051996:Transcription Factor RelA; D015533:Transcriptional Activation / Q000502:physiology*; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D051020:bcl-X Protein