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


CONCLUSIONS
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.
Ji
Guo-Zhong
GZ
Department of Gastroenterology, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China. jgzzl@163.co
Wang
Xue-Hao
XH
Miao
Lin
L
Liu
Zheng
Z
Zhang
Ping
P
Zhang
Fa-Ming
FM
Yang
Jian-Bing
JB
D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000378:metabolism*; D016328:NF-kappa B / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology*; D051901:Smad4 Protein / Q000032:analysis / Q000502:physiology*; D051906:Smad7 Protein / Q000032:analysis / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D016328:NF-kappa B; D018125:Receptors, Transforming Growth Factor beta; C497796:SMAD4 protein, human; C497806:SMAD7 protein, human; D051901:Smad4 Protein; D051906:Smad7 Protein; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II