Yu Hong-Gang, Yu Liang-Liang, Yang Yanning, Luo He-Sheng, Yu Jie-Ping, Meier Juris J, Schrader Henning, Bastian Andreas, Schmidt Wolfgang E, Schmitz Frank
Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan, China.
Oncology. 2003;65(1):37-45. doi: 10.1159/000071203.
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.
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.
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.
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.
为明确凋亡重要抑制因子RelA/核因子-κB在结直肠癌发生中的作用，我们检测了RelA在正常结直肠黏膜（n = 10）、结直肠腺瘤（n = 30）和结直肠腺癌（n = 30）中的表达。此外，还研究了RelA表达与肿瘤细胞凋亡、增殖以及Bcl-2/Bcl-x(L)表达之间的关联。
用针对RelA、Bcl-2、Bcl-x(L)和Ki-67的单克隆抗体对石蜡切片进行染色，以评估正常、腺瘤性和结肠癌组织中的蛋白表达模式。使用原位检测试剂盒通过末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法（TUNEL）检测凋亡细胞。
免疫组织化学染色结果显示，从低级别发育异常腺瘤向腺癌转变过程中，RelA、Bcl-2、Bcl-x(L)的表达以及Ki-67标记指数（LI）显著增加。这种转变与凋亡指数（AI）显著降低以及Ki-67 LI显著增加相关。在从低级别发育异常向腺癌转变过程中，RelA的表达与AI呈负相关，与Bcl-2、Bcl-x(L)的表达以及Ki-67 LI呈正相关。
我们的结果表明，RelA/核因子-κB表达增加在人类结肠癌发病机制中从低级别发育异常结直肠腺瘤向腺癌的转变过程中起重要作用。
