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首页> 外文期刊>Oncogene >Involvement of programmed cell death 4 in transforming growth factor-|[beta]|1-induced apoptosis in human hepatocellular carcinoma
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Involvement of programmed cell death 4 in transforming growth factor-|[beta]|1-induced apoptosis in human hepatocellular carcinoma

机译:程序性细胞死亡4与转化生长因子-|β| 1-诱导的人肝细胞癌的凋亡有关

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The programmed cell death 4 (PDCD4) gene was originally identified as a tumor-related gene in humans and acts as a tumor-suppressor in mouse epidermal carcinoma cells. However, its function and regulatory mechanisms of expression in human cancer remain to be elucidated. We therefore investigated the expression of PDCD4 in human hepatocellular carcinoma (HCC) and the role of PDCD4 in human HCC cells. Downregulation of PDCD4 protein was observed in all HCC tissues tested compared with corresponding noncancerous liver, as revealed by Western blotting or immunohistochemical staining. Human HCC cell line, Huh7, transfected with PDCD4 cDNA showed nuclear fragmentation and DNA laddering characteristic of apoptotic cells associated with mitochondrial changes and caspase activation. Transforming growth factor-1 (TGF-1) treatment of Huh7 cells resulted in increased PDCD4 expression and occurrence of apoptosis, also concomitant with mitochondrial events and caspase activation. Transfection of Smad7, a known antagonist to TGF-1 signaling, protected cells from TGF-1-mediated apoptosis and suppressed TGF-1-induced PDCD4 expression. Moreover, antisense PDCD4 transfectants were resistant to apoptosis induced by TGF-1. In conclusion, these data suggest that PDCD4 is a proapoptotic molecule involved in TGF-1-induced apoptosis in human HCC cells, and a possible tumor suppressor in hepatocarcinogenesis.
机译:程序性细胞死亡4(PDCD4)基因最初被鉴定为人类中与肿瘤相关的基因,并在小鼠表皮癌细胞中充当肿瘤抑制因子。然而,其在人类癌症中的功能和表达的调控机制仍有待阐明。因此,我们研究了PDCD4在人肝细胞癌(HCC)中的表达以及PDCD4在人HCC细胞中的作用。 Western blotting或免疫组织化学染色显示,与相应的非癌性肝相比,在所有测试的HCC组织中均观察到PDCD4蛋白的下调。用PDCD4 cDNA转染的人类HCC细胞系Huh7显示出与线粒体变化和caspase激活相关的凋亡细胞的核片段化和DNA阶梯化特征。转化生长因子-1(TGF-1)处理的Huh7细胞导致PDCD4表达增加和细胞凋亡的发生,还伴随着线粒体事件和caspase活化。 Smad7(一种已知的TGF-1信号拮抗剂)的转染可保护细胞免受TGF-1介导的细胞凋亡并抑制TGF-1诱导的PDCD4表达。而且,反义PDCD4转染子对TGF-1诱导的细胞凋亡具有抗性。总之,这些数据表明,PDCD4是一种促凋亡分子,参与TGF-1诱导的人HCC细胞凋亡,并且可能是肝癌发生中的肿瘤抑制因子。

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