Mizutani Kazunori, Miyamoto Shizuyo, Nagahata Takemitsu, Konishi Noboru, Emi Mitsuru, Onda Masamitsu
Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan.
Tumori. 2005 Nov-Dec;91(6):546-51. doi: 10.1177/030089160509100616.
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 Wnt/beta-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.
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.
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.
DVL1 was overexpressed in prostate cancer and its overexpression might be related to prostate cancer progression through the Wnt/beta-catenin pathway.
Wnt/β-连环蛋白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,DVL1基因被鉴定为Wnt/β-连环蛋白信号通路的一个中间分子。此外,在乳腺癌和宫颈癌中已报道有DVL1基因的改变。前列腺癌中β-连环蛋白的异常已得到充分研究,因此对前列腺癌中DVL1基因的检测很有吸引力。
我们通过半定量PCR(SQ-PCR)研究了20例原发性前列腺癌中DVL1信使核糖核酸的改变,并通过免疫组织化学分析评估了同一样本中的蛋白表达。此外,用一组新的经验证的20例前列腺癌评估了DVL1和β-连环蛋白的蛋白表达。
SQ-PCR显示前列腺癌中DVL1有显著过表达(65%)。免疫染色证实前列腺癌中DVL1基因产物上调。通过SQ-PCR和免疫染色,所有病例均未显示DVL1表达不足或下调。此外,数据显示DVL1信使核糖核酸与蛋白表达之间存在相关性。有趣的是,DVL1的表达水平随组织学分级恶化而升高。此外,证实了DVL1表达与β-连环蛋白表达之间存在相关性。
DVL1在前列腺癌中过表达,其过表达可能通过Wnt/β-连环蛋白途径与前列腺癌进展相关。