转化生长因子-β1-Smad信号转导通路在肝细胞癌患者中的作用

Role of transforming growth factor-beta1-smad signal transduction pathway in patients with hepatocellular carcinoma.

作者信息

Ji Guo-Zhong, Wang Xue-Hao, Miao Lin, Liu Zheng, Zhang Ping, Zhang Fa-Ming, Yang Jian-Bing

机构信息

Department of Gastroenterology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China.

出版信息

World J Gastroenterol. 2006 Jan 28;12(4):644-8. doi: 10.3748/wjg.v12.i4.644.

DOI:10.3748/wjg.v12.i4.644

PMID:16489684

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4066103/

Abstract

AIM

To explore the role of transforming growth factor-beta1 (TGF-beta1)-smad signal transduction pathway in patients with hepatocellular carcinoma.

METHODS

Thirty-six hepatocellular carcinoma specimens were obtained from Qidong Liver Cancer Institute and Department of Pathology of the Second Affiliated Hospital of Nanjing Medical University. All primary antibodies (polyclonal antibodies) to TGF-beta1, type II Transforming growth factor-beta receptor (TbetaR-II), nuclear factor-kappaB (NF-kappaB), CD34, smad4 and smad7,secondary antibodies and immunohistochemical kit were purchased from Zhongshan Biotechnology Limited Company (Beijing, China). The expressions of TGF-beta1, TbetaR-II, NF-kappaB, smad4 and smad7 proteins in 36 specimens of hepatocellular carcinoma (HCC) and its adjacent tissue were separately detected by immunohistochemistry to observe the relationship between TGF-beta1 and TbetaR-II, between NF-kappaB and TGF-beta1, between smad4 and smad7 and between TGF-beta1 or TbetaR-IIand microvessel density (MVD). MVD was determined by labelling the vessel endothelial cells with CD34.

RESULTS

The expression of TGF-beta1, smad7 and MVD was higher in HCC tissue than in adjacent HCC tissue (P<0.01, P<0.05, P<0.01 respectively). The expression of TbetaR-IIand smad4 was lower in HCC tissue than in its adjacent tissue (P<0.01, P<0.05 respectively). The expression of TGF-beta1 protein and NF-kappaB protein was consistent in HCC tissue. The expression of TGF-beta1 and MVD was also consistent in HCC tissue. The expression of TbetaR-IIwas negatively correlated with that of MVD in HCC tissue.

CONCLUSION

The expressions of TGF-beta1, TbetaR-II, NF-kappaB, smad4 and smad7 in HCC tissue, which are major up and down stream factors of TGF-beta1-smad signal transduction pathway , are abnormal. These factors are closely related with MVD and may play an important role in HCC angiogenesis. The inhibitory action of TGF-beta1 is weakened in hepatic carcinoma cells because of abnormality of TGF-beta1 receptors (such as TbetaR-II) and postreceptors (such as smad4 and smad7). NF-kappaB may cause activation and production of TGF-beta1.

摘要

目的

探讨转化生长因子-β1（TGF-β1）-smad信号转导通路在肝细胞癌患者中的作用。

方法

从启东肝癌研究所和南京医科大学第二附属医院病理科获取36例肝细胞癌标本。所有针对TGF-β1、Ⅱ型转化生长因子-β受体（TβR-II）、核因子-κB（NF-κB）、CD34、smad4和smad7的一抗（多克隆抗体）、二抗及免疫组织化学试剂盒均购自中山生物技术有限公司（中国北京）。采用免疫组织化学方法分别检测36例肝细胞癌（HCC）及其癌旁组织中TGF-β1、TβR-II、NF-κB、smad4和smad7蛋白的表达，观察TGF-β1与TβR-II之间、NF-κB与TGF-β1之间、smad4与smad7之间以及TGF-β1或TβR-II与微血管密度（MVD）之间的关系。通过用CD34标记血管内皮细胞来测定MVD。

结果

HCC组织中TGF-β1、smad7的表达及MVD均高于癌旁组织（分别为P<0.01、P<0.05、P<0.01）。HCC组织中TβR-II和smad4的表达低于其癌旁组织（分别为P<0.01、P<0.05）。HCC组织中TGF-β1蛋白与NF-κB蛋白的表达一致。HCC组织中TGF-β1与MVD的表达也一致。HCC组织中TβR-II的表达与MVD呈负相关。

结论

HCC组织中TGF-β1-smad信号转导通路的主要上下游因子TGF-β1、TβR-II、NF-κB、smad4和smad7的表达异常。这些因子与MVD密切相关，可能在HCC血管生成中起重要作用。由于TGF-β1受体（如TβR-II）和受体后分子（如smad4和smad7）异常，TGF-β1在肝癌细胞中的抑制作用减弱。NF-κB可能导致TGF-β1的激活和产生。