Upregulation and overexpression of DVL1, the human counterpart of the Drosophila dishevelled gene, in prostate cancer
Upregulation and overexpression of DVL1, the human counterpart of the Drosophila dishevelled gene, in prostate cancer
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DOI：
10.1177/030089160509100616
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发表时间：
2005-11-01
期刊：
影响因子：
1.9
通讯作者：
Onda, Masamitsu
中科院分区：
文献类型：
--
作者：
Mizutani, Kazunori;Miyamoto, Shizuyo;Onda, Masamitsu
目的和背景：Wnt/β-catenin信号通路是包括前列腺癌在内的人类恶性肿瘤的主要致癌机制之一。最近，DVL 1基因被鉴定为WnV β-连环蛋白信号通路的中间分子。此外，在乳腺癌和宫颈癌中已经报道了DVL 1基因的改变。方法：采用半定量PCR（SQ-PCR）方法检测20例前列腺癌组织中DVL 1 mRNA的表达，并采用免疫组化方法检测DVL 1蛋白的表达。此外，DVL 1和β-catenin蛋白的表达进行了评估与一个新的验证集20前列腺癌。结果：SQ-PCR显示显着的DVL 1过表达的前列腺癌（65%）。通过免疫染色证实了前列腺癌中DVL 1基因产物的上调。SQ-PCR和免疫组化结果显示，所有病例均未出现DVL 1的低表达或下调。此外，数据显示DVL 1 mRNA和蛋白表达之间的相关性。有趣的是，DVL 1的表达水平随着组织学分级的恶化而增加。结论：DVL 1在前列腺癌组织中过表达，其过表达可能通过Wnt/beta-catenin途径参与前列腺癌的发生、发展。
Aims and background: The Wnt/beta-catenin signaling pathway is one of the main carcinogenic mechanisms in human malignancies including prostate cancer. Recently, the DVL1 gene was identified as a middle molecule of the WnVbeta-catenin signaling pathway. In addition, alterations of the DVL1 gene have been reported in breast and cervical cancer. The abnormality of beta-catenin in prostate cancer has been well studied, so the examination of the DVL1 gene in prostate cancer is appealing.Methods: We investigated DVL1 messenger RNA alterations by semiquantitative PCR (SQ-PCR) in 20 primary prostate cancers and assessed the protein expression by immunohistochemical analysis in the same samples. In addition, DVL1 and beta-catenin protein expression was evaluated with a new validated set of 20 prostate cancers.Results: SQ-PCR revealed significant overexpression of DVL1 in prostate cancer (65%). Upregulation of the DVL1 gene product in prostate cancer was confirmed by immunostaining. With SQ-PCR and immunostaining, none of the cases showed underexpression or downregulation of DVL1. In addition, the data showed correlations between DVL1 mRNA and protein expression. Interestingly, the expression level of DVL1 increased with worsening histological grade. In addition, a correlation between DVL1 expression and beta-catenin expression was confirmed.Conclusions: DVL1 was overexpressed in prostate cancer and its overexpression might be related to prostate cancer progression through the Wnt/beta-catenin pathway.