Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma
Tensin2 variant 3 is associated with aggressive tumor behavior in human hepatocellular carcinoma
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DOI：
10.1002/hep.21339
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发表时间：
2006-10-01
期刊：
影响因子：
13.5
通讯作者：
Ng, Irene Oi-Lin
中科院分区：
文献类型：
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作者：
Yam, Judy Wai Ping;Ko, Frankie Chi Fat;Ng, Irene Oi-Lin
张力蛋白是一个新的蛋白质家族，在细胞外基质、肌动蛋白细胞骨架和信号转导之间起着重要的联系作用，并且与人类癌症有关。张力蛋白2最初是在寻找与张力蛋白I具有广泛序列同源性的新的张力蛋白家族成员中鉴定的。Tensin 2在肝组织中高表达。最近的一项研究报道，tensin 2的剪接变体之一，变体3，促进细胞迁移。在本研究中，我们的目的是阐明变异3在肝癌发生中的作用，通过评估变异3 mRNA在肝细胞癌（HCC）组织中的表达和异位表达变异3在HCC细胞系。对人肝癌组织中变异体3表达的分析显示，与相应的非肿瘤性肝脏相比，它在46%（23/50）的肿瘤组织中过表达。变异体3的高表达与静脉浸润（P = 0.037）、肿瘤微卫星形成（P = 0.022）和肿瘤无包膜（P = 0.049）显著相关。我们的异位表达研究表明，变异体3显着促进肝癌细胞的细胞生长和运动。变体3的克隆转染子比对照载体转染子更紧密地堆积并导致更高的饱和密度。变体3的表达还增强了培养物中的增殖率和裸鼠体内的致瘤性。总之，我们揭示了变异体3在肝癌进展中的新作用，并提出了变异体3表达升高作为肝癌肿瘤进展标志物的可行性。
Tensins are a new family of proteins that act as an important link among extracellular matrix, actin cytoskeleton, and signal transduction and have been implicated in human cancers. Tensin2 was initially identified in a search for new tensin family members that share extensive sequence homology with tensin I. Tensin2 was highly expressed in liver tissues. A recent study reported that one of the splicing variants of tensin2, variant 3, promotes cell migration. In the present study, we aimed to elucidate the role of variant 3 in hepatocarcinogenesis by assessing the expression of variant 3 mRNA in hepatocellular carcinoma (HCC) tissue and ectopically expressing variant 3 in HCC cell lines. Analysis of variant 3 expression in human HCC tissue revealed it was overexpressed in 46% (23/50) of tumor tissues as compared with the corresponding nontumorous livers. High expression of variant 3 was significantly associated with venous invasion (P = .037), tumor microsatellite formation (P = .022), and tumor nonencapsulation (P = .049). Our ectopic expression study showed that variant 3 significantly promoted the cell growth and motility of HCC cells. The clonal transfectants of variant 3 were more closely packed and resulted in a higher saturation density than in the control vector transfectants. Variant 3 expression also enhanced the proliferation rate in culture and in vivo tumorigenicity in nude mice. In conclusion, we reveal a novel role for variant 3 in the progression of HCC and suggest the feasibility of elevated variant 3 expression as a tumor progression marker for HCC.