Dickkopf-1 is overexpressed in human pancreatic ductal adenocarcinoma cells and is involved in invasive growth
Dickkopf-1 is overexpressed in human pancreatic ductal adenocarcinoma cells and is involved in invasive growth
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DOI：
10.1002/ijc.24865
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发表时间：
2010-04-01
影响因子：
6.4
通讯作者：
Kataoka, Hiroaki
中科院分区：
文献类型：
--
作者：
Takahashi, Nobuyasu;Fukushima, Tsuyoshi;Kataoka, Hiroaki
Dickkopf（DKK）基因的蛋白产物是Writ糖蛋白的拮抗剂，其通过结合卷曲受体参与肿瘤的发展和进展。在这项研究中，DKK-1的表达进行了分析，在一组43人培养的癌细胞系。DKK-1表达在胰腺癌细胞系中持续显著上调。DKK-3的表达水平也较低。相反，DKK-2和-4在大多数胰腺癌细胞系中不表达。在手术切除的人胰腺癌组织中证实了DKK-1的过表达，其中在来自癌性和非癌性胰腺组织的配对样品中评估了mRNA水平。在导管腺癌（23例），DKK-1 mRNA水平显着上调相比，相应的非癌组织在统计学上的显着水平。为了测试DKK-1在胰腺癌细胞中的生物学作用，我们使用逆转录病毒短发夹RNA表达载体在SUIT-2人胰腺癌细胞系及其转移性亚系S2-CP 8中进行DKK-1的敲低。DKK-1敲低导致SUIT-2在体外的迁移活性降低。在S2-CP 8细胞中，DKK-1敲低也抑制了体外生长速率和Matrigel侵袭。总的来说，这些证据表明，尽管DKK-1在Writ信号传导中具有假定的拮抗作用，但它可能在胰腺癌细胞的侵袭性中发挥作用，因此可以作为胰腺癌的新生物标志物。
The protein products of the Dickkopf (DKK) genes are antagonists of Writ glycoproteins, which participate in tumor development and progression by binding to frizzled receptors. In this study, the expression of DKK-1 was analyzed in a panel of 43 human cultured carcinoma cell lines. DKK-1 expression was consistently and significantly upregulated in pancreatic carcinoma cell lines. Low level of DKK-3 expression was also seen. In contrast, the expression of DKK-2 and -4 was not detectable in most pancreatic carcinoma cell lines. The overexpression of DKK-1 was confirmed in surgically resected human pancreatic cancer tissues, in which the mRNA level was evaluated in paired samples from cancerous and noncancerous pancreatic tissues. In ductal adenocarcinomas (23 cases), DKK-1 mRNA levels were significantly upregulated compared to corresponding noncancerous tissues in a statistically significant level. To test the biological role of DKK-1 in pancreatic carcinoma cells, we performed a knockdown of DKK-1 in SUIT-2 human pancreatic adenocarcinoma cell line and S2-CP8, its metastatic subline, using a retroviral short hairpin RNA expression vector. DKK-1 knockdown resulted in reduced migratory activity of SUIT-2 in vitro. The in vitro growth rate and Matrigel invasion were also suppressed by DKK-1 knockdown in S2-CP8 cells. Collectively, the evidence suggests that, despite of its presumed antagonistic role in Writ signaling, DKK-1 may have a role in the aggressiveness of pancreatic carcinoma cells and could, therefore, serve as a novel biomarker of pancreatic cancer.