Des-gamma-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma.
Des-gamma-carboxy prothrombin is a potential autologous growth factor for hepatocellular carcinoma.
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发表时间：
2005
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通讯作者：
Mayumi Suzuki;H. Shiraha;Tatsuya Fujikawa;N. Takaoka;N. Ueda;Y. Nakanishi;K. Koike;A. Takaki;Y. Shiratori
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作者：
Mayumi Suzuki;H. Shiraha;Tatsuya Fujikawa;N. Takaoka;N. Ueda;Y. Nakanishi;K. Koike;A. Takaki;Y. Shiratori
DES-γ-羧基凝血酶原(DCP)是公认的肝细胞癌的肿瘤标志物。在本研究中，我们证明了DCP对肝癌细胞系具有促有丝分裂作用。纯化的DCP以剂量依赖方式刺激Hep3B和SK-Hep-1细胞DNA合成。DCP可与细胞表面受体Met结合，引起Met自身磷酸化，并通过Janus kinase1激活STAT3信号通路。荧光素酶基因报告分析表明，DCP可诱导STAT3相关转录。针对STAT3和Met的小干扰RNA可阻断DCP诱导的细胞增殖。DCP不影响丝裂原活化蛋白激酶通路、Myc信号通路或肌醇磷脂3-激酶/Akt通路。基于这些结果，我们认为DCP可以作为肝癌细胞系的自体有丝分裂原。Met-Janus kinase1-STAT3信号通路可能是DCP诱导细胞增殖的主要信号通路。
Des-gamma-carboxyl prothrombin (DCP) is a well recognized tumor marker for hepatocellular carcinoma (HCC). In the present study, we demonstrate that DCP has a mitogenic effect on HCC cell lines. Purified DCP stimulated DNA synthesis of Hep3B and SK-Hep-1 cells in a dose-dependent manner. DCP was found to bind with cell surface receptor Met causing Met autophosphorylation and also to activate STAT3 signaling pathway through Janus kinase 1. Luciferase gene reporter analysis showed that DCP induced STAT3-related transcription. Small interfering RNAs against both STAT3 and Met abrogated DCP-induced cell proliferation. DCP did not affect the mitogen-activated protein kinase pathway, Myc signaling pathway, or phosphoinositide 3-kinase/Akt pathway. Based on these results, we believe that DCP acts as an autologous mitogen for HCC cell lines. The Met-Janus kinase 1-STAT3 signaling pathway may be a major signaling pathway for DCP-induced cell proliferation.