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首页> 外文期刊>Acta Biochimica et Biophysica Sinica >Human tetraspanin transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein is overexpressedn in hepatocellular carcinoma and accelerates tumor cell growth
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Human tetraspanin transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein is overexpressedn in hepatocellular carcinoma and accelerates tumor cell growth

机译:人四跨膜蛋白跨膜4超家族成员4或肠和肝四跨膜蛋白在肝细胞癌中过表达并加速肿瘤细胞的生长

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摘要

The human transmembrane 4 superfamily member 4 or intestinal and liver tetraspan membrane protein (TM4SF4/il-TMP) was originally cloned as an intestinal and liver tetraspan membrane protein and mediates density-dependent cell proliferation. The rat homolog of TM4SF4 was found to be up-regulated in regenerating liver after two-thirds hepatectomy and overexpression of TM4SF4 could enhance liver injury induced by CCl4. However, the expression and significance of TM4SF4/il-TMP in liver cancer remain unknown. Here, we report that TM4SF4/il-TMP is frequently and significantly overexpressed in hepatocellular carcinoma (HCC). Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis showed that TM4SF4/il-TMP mRNA and protein levels were up-regulated in ∼80% of HCC tissues. Immunohistochemical analysis of a 75 paired HCC tissue microarray revealed that TM4SF4/il-TMP was significantly overexpressed in HCC tissues (P< 0.001), and high immunointensity of TM4SF4/il-TMP tended to be in well-to-moderately differentiated HCC compared with poorly differentiated tumors. Functional studies showed that overexpression of TM4SF4/il-TMP in QGY-7701 and BEL-7404 HCC cell lines through stable transfection of TM4SF4 expression plasmid significantly promoted both cell growth and colony formation of HCC cells. Reduction of TM4SF4/il-TMP expression in QGY-7701 and BEL-7404 cells by stably transfecting TM4SF4 antisense plasmid caused great inhibition of cell proliferation. Our findings suggest that TM4SF4/il-TMP has the potential to be biomarker in HCC and plays a crucial role in promotion of cancer cell proliferation.
机译:人跨膜4超家族成员4或肠和肝四跨膜蛋白(TM4SF4 / il-TMP)最初被克隆为肠和肝四跨膜蛋白并介导密度依赖性细胞增殖。三分之二的肝切除术后,再生肝中大鼠TM4SF4同源蛋白被上调,而TM4SF4的过表达可增强CCl 4 引起的肝损伤。然而,TM4SF4 / il-TMP在肝癌中的表达和意义仍然未知。在这里,我们报道TM4SF4 / il-TMP在肝细胞癌(HCC)中频繁且明显过表达。实时定量逆转录聚合酶链反应(RT-PCR)和Western印迹分析表明,约80%的HCC组织中TM4SF4 / il-TMP mRNA和蛋白质水平上调。对75个配对的HCC组织芯片的免疫组织化学分析显示,TM4SF4 / il-TMP在HCC组织中显着过表达(P <0.001),TM4SF4 / il-TMP的高免疫强度倾向于在与中度分化良好的HCC相比低分化肿瘤。功能研究表明,通过稳定转染TM4SF4表达质粒,QGY-7701和BEL-7404 HCC细胞系中TM4SF4 / il-TMP的过表达显着促进了HCC细胞的生长和集落形成。通过稳定转染TM4SF4反义质粒减少QGY-7701和BEL-7404细胞中TM4SF4 / il-TMP表达,从而大大抑制了细胞增殖。我们的发现表明,TM4SF4 / il-TMP在肝癌中具有成为生物标志物的潜力,并且在促进癌细胞增殖中起着至关重要的作用。

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  • 来源
    《Acta Biochimica et Biophysica Sinica》 |2012年第3期|p.224-232|共9页
  • 作者

    Mujun Zhao;

  • 作者单位

    , Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, @%@, Institut Pasteur, @%@Correspondence address. Tel: +@%@;

    Fax: +@%@;

    E-mail:;

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