Expression of WISPs and of their novel alternative variants in human hepatocellular carcinoma cells
Expression of WISPs and of their novel alternative variants in human hepatocellular carcinoma cells
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DOI：
10.1196/annals.1322.051
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Montalto, G
中科院分区：
文献类型：
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作者：
Cervello, M;Giannitrapani, L;Montalto, G
WISP（Wnt诱导的分泌蛋白）是CCN（CTGF/Cyr 61/Nov）家族的成员，其参与纤维化疾病和肿瘤发生。它们具有由四个保守的富含半胱氨酸的模块化结构域组成的典型结构，但是在各种病理条件下已经描述了通过选择性剪接或基因突变产生的缺少一个或多个模块的CCN成员的变体。WISP基因首先被描述为Wnt信号通路的下游靶标，该通路在人肝细胞癌（HCC）中经常改变。在本研究中，WISP mRNA的表达通过RT-PCR分析在四个人肝癌细胞系（HepG 2，HuH-6，HuH-7，HA 22 T/VGH）。我们的研究结果首次表明，WISP 1，WISP 1v和WISP 3在HCC细胞系中表达。此外，我们鉴定了两种新的变体，分别由WISP 1和WISP 3的选择性剪接产生，命名为WISP 1 Delta ex 3 -4和WISP 3v（L）。总的来说，我们的研究表明，WISP转录可能在HCC的发展中发挥作用，尽管需要进一步的研究来阐明野生型WISP及其新变体在这种肿瘤类型中表达的相对重要性。
WISPs (Wnt-induced secreted proteins) are members of the CCN (CTGF/Cyr61/Nov) family involved in fibrotic disorders and tumorigenesis. They have a typical structure composed of four conserved cysteine-rich modular domains, but variants of CCN members lacking one or more modules, generated by alternative splicing or gene mutations, have been described in various pathological conditions. WISP genes were first described as downstream targets of the Wnt signaling pathway, which is frequently altered in human hepatocellular carcinoma (HCC). In the present study, WISP mRNA expression was analyzed by RT-PCR in four human HCC cell lines (HepG2, HuH-6, HuH-7, HA22T/VGH). Our results show for the first time that WISP1, WISP1v, and WISP3 are expressed in HCC cell lines. Moreover, we identified two novel variants, generated by alternative splicing of WISP1 and WISP3, respectively, named WISP1 Delta ex3-4 and WISP3v(L). Overall, our study suggests that WISP transcripts may have a role in the development of HCC, although further studies are necessary to clarify the relative importance of the expression of wild-type WISPs, as well as of their novel variants, in this tumor type.