Kuphal S, Lodermeyer S, Bataille F, Schuierer M, Hoang B H, Bosserhoff A K
Institute of Pathology, University Regensburg, Regensburg, Germany.
Oncogene. 2006 Aug 17;25(36):5027-36. doi: 10.1038/sj.onc.1209508. Epub 2006 Mar 27.
The Dickkopf (DKK) genes were originally identified as factors inducing head formation in Xenopus. The genes code for inhibitors that are involved in Wnt signaling. We speculate that loss of DKK expression plays a role in development or progression of malignant melanoma. Thus, we evaluated melanoma cell lines and tissue samples of malignant melanoma for loss of DKK, especially DKK-3 transcription. We found that DKK-1, -2 and -3 were downregulated or lost in all cell lines and in most of the tumor samples analysed. Reduced DKK-3 expression occurred as early as in primary tumors detected by both immunohistochemical and reverse transcription-polymerase chain reaction RT-PCR analysis. Functional assays with stable DKK-3 transfected cell lines revealed that DKK-3 expression increased cell-cell adhesion and decreased cell migration. Further, downregulation of fibronectin, snail-1 and re-expression of E-cadherin was found in the DKK-3 expressing cell clones supporting a role of DKK-3 in tumor progression. Our studies thus indicate that loss of DKK-3 expression may contribute to melanoma progression.
Dickkopf（DKK）基因最初被鉴定为在非洲爪蟾中诱导头部形成的因子。这些基因编码参与Wnt信号传导的抑制剂。我们推测DKK表达缺失在恶性黑色素瘤的发生或发展中起作用。因此，我们评估了黑色素瘤细胞系和恶性黑色素瘤组织样本中DKK的缺失情况，尤其是DKK-3的转录情况。我们发现，在所有分析的细胞系和大多数肿瘤样本中，DKK-1、-2和-3均下调或缺失。通过免疫组织化学和逆转录聚合酶链反应（RT-PCR）分析发现，DKK-3表达降低早在原发性肿瘤中就已出现。对稳定转染DKK-3的细胞系进行的功能分析表明，DKK-3表达增加了细胞间黏附并减少了细胞迁移。此外，在表达DKK-3的细胞克隆中发现纤连蛋白、蜗牛蛋白-1下调以及E-钙黏蛋白重新表达，这支持了DKK-3在肿瘤进展中的作用。因此，我们的研究表明DKK-3表达缺失可能促进黑色素瘤进展。
