Increased expression of RelA/nuclear factor-kappa B protein correlates with colorectal tumorigenesis.
OBJECTIVE
To identify the role of RelA/nuclear factor-kappa B, an important inhibitor of apoptosis in colorectal tumorigenesis, we examined the expression of RelA in normal colorectal mucosa (n = 10), colorectal adenomas (n = 30) and colorectal adenocarcinomas (n = 30). Furthermore, the association of RelA expression with tumor cell apoptosis, proliferation, and expression of Bcl-2/Bcl-x(L )was also studied.


METHODS
Paraffin sections were stained with monoclonal antibodies directed against RelA, Bcl-2, Bcl-x(L), and Ki-67 to assess protein expression patterns in normal, adenomatous and colon cancer tissue. Apoptotic cells were detected by terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) using an in situ detection kit.


RESULTS
The results of immunohistochemical staining revealed that expression of RelA, Bcl-2, Bcl-x(L), and Ki-67 labeling index (LI) significantly increased in the transition from adenoma with low dysplasia to adenocarcinoma. This transition was associated with a significant decrease in the apoptotic index (AI) and a significant increase in the Ki-67 LI. The expression of RelA correlated inversely with the AI and correlated positively with the expression of Bcl-2, Bcl-x(L), and Ki-67 LI in the transition from low-grade dysplasia to adenocarcinoma.


CONCLUSIONS
Our results suggest that increased expression of RelA/nuclear factor-kappa B plays an important role in the transition from colorectal adenoma with low-grade dysplasia to adenocarcinoma in the pathogenesis of colon cancer in humans.
Yu
Hong-Gang
HG
Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan, China.
Yu
Liang-Liang
LL
Yang
Yanning
Y
Luo
He-Sheng
HS
Yu
Jie-Ping
JP
Meier
Juris J
JJ
Schrader
Henning
H
Bastian
Andreas
A
Schmidt
Wolfgang E
WE
Schmitz
Frank
F
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D016612:Paraffin Embedding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051996:Transcription Factor RelA; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019394:Ki-67 Antigen; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D051996:Transcription Factor RelA; D051020:bcl-X Protein