AIM: To explore the role of transforming growth factorbeta1 (TGF-β1)-smad signal transduction pathway in patients with hepatocellular carcinoma. METHODS: Thirty-six hepatocellular carcinoma specimens were obtaine...AIM: To explore the role of transforming growth factorbeta1 (TGF-β1)-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-β1, type H Transforming growth factor-beta receptor (TβR-Ⅱ), nuclear factor-kappaB (NF-KB), CD34, smad4 and smad7, secondary antibodies and immunohistochemical kit were purchased from Zhongshan Biotechnology Limited Company (Beijing, China). The expressions of TGF-β1, TβR-Ⅱ, NF- KB, 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-β1 and TβR-Ⅱ, between NF-KB and TGF-β1, between smad4 and smad7 and between TGF-β1 or TβR-Ⅱ and microvessel density (MVD). MVD was determined by labelling the vessel endothelial cells with CD34. RESULTS: The expression of TGF-β1, 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 TβR-Ⅱ and smad4 was lower in HCC tissue than in its adjacent tissue (P〈0.01, P〈0.05 respectively). The expression of TGF-β1 protein and NF-KB protein was consistent in HCC tissue. The expression of TGF-β1 and MVD was also consistent in HCC tissue. The expression of TIER- Ⅱ was negatively correlated with that of MVD in HCC tissue. CONCLUSION: The expressions of TGF-IB1, TβR- Ⅱ, NF-KB, smad4 and smad7 in HCC tissue, which are major up and down stream factors of TGF-β1-smad signal transduction pathway, are abnormal. These factors are closely related with NVD and may play an important role in HCC angiogenesis. The inhibitory action of TGF-β1 is weakened in hepatic carcinoma cells because of abnormality of TGF-β1 receptors (such as TIBR- Ⅱ) and postreceptors (such as smad4 and smad7). NF-KB may cause activation and production of TGF-β1.展开更多
基金Supported by Natural Science Foundation of Jiangsu Province, No. BK2001168 Natural Science Foundation of Department of Education of Jiangsu Province, No. 02KJD320023 Science and Technology Innovation Foundation of Nanjing Medical University, No. CX2004004.
文摘AIM: To explore the role of transforming growth factorbeta1 (TGF-β1)-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-β1, type H Transforming growth factor-beta receptor (TβR-Ⅱ), nuclear factor-kappaB (NF-KB), CD34, smad4 and smad7, secondary antibodies and immunohistochemical kit were purchased from Zhongshan Biotechnology Limited Company (Beijing, China). The expressions of TGF-β1, TβR-Ⅱ, NF- KB, 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-β1 and TβR-Ⅱ, between NF-KB and TGF-β1, between smad4 and smad7 and between TGF-β1 or TβR-Ⅱ and microvessel density (MVD). MVD was determined by labelling the vessel endothelial cells with CD34. RESULTS: The expression of TGF-β1, 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 TβR-Ⅱ and smad4 was lower in HCC tissue than in its adjacent tissue (P〈0.01, P〈0.05 respectively). The expression of TGF-β1 protein and NF-KB protein was consistent in HCC tissue. The expression of TGF-β1 and MVD was also consistent in HCC tissue. The expression of TIER- Ⅱ was negatively correlated with that of MVD in HCC tissue. CONCLUSION: The expressions of TGF-IB1, TβR- Ⅱ, NF-KB, smad4 and smad7 in HCC tissue, which are major up and down stream factors of TGF-β1-smad signal transduction pathway, are abnormal. These factors are closely related with NVD and may play an important role in HCC angiogenesis. The inhibitory action of TGF-β1 is weakened in hepatic carcinoma cells because of abnormality of TGF-β1 receptors (such as TIBR- Ⅱ) and postreceptors (such as smad4 and smad7). NF-KB may cause activation and production of TGF-β1.