Upregulation and Overexpression of DVL1, the Human Counterpart of the Drosophila Dishevelled Gene, in Prostate Cancer

Abstract

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 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. 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.

Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin

“…The involvement of DVLs in invasive ductal carcinoma of the breast was also reported by Prasad et al [30]. Mizutani et al [31] got similar results in prostate cancer. Their sample of 20 primary prostate cancer showed significant over expression of DVL1 (65%) and correlation to beta-catenin’s expression.…”

Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression

“…Collectively, our findings suggest that Dvl family members may be essential for the development and progression of NSCLCs but may function through differential mechanisms. By immunohistochemistry, Dvl-1 has been shown to be expressed in human breast cancers, prostate cancers and cervical squamous carcinomas, with expression incidences of around 50% [22][23][24]. Our present study presents an expression incidence of 36.3% for Dvl-1 in 113 NSCLC [26] demonstrated by immunoblotting that six out of eight NSCLCs expressed Dvl-3 protein, whereas Dvl-1 and Dvl-2 proteins were undetectable.…”

“…Therefore, the three members of the Dvl family may be essential for the de-differentiation of tumor cells in lung cancers. Dvl-1 protein has been reported to be expressed exclusively in tumor cells but not in normal epithelial cells in breast cancers, cervical squamous carcinomas or prostate cancers [22][23][24]. In a recent report on colon cancers, Dvl-1 protein was expressed specifically in cancer tissues and not in normal mucosa, whereas Dvl-2 and Dvl-3 proteins were detected in both cancerous and normal tissues [40].…”

“…We counted 400 tumor cells and calculated the percentage of positive staining cells. We used the criteria for scoring described by Mizutani et al [24] with slight modifications: 0, no staining; 1, 1-10% positive; 2, 11-25% positive; 3, 26-50% positive; 4, >50% positive. Sections were classified into two groups: negative expression (with a score of 0 or 1) and positive expression (with a score of 2, 3 or 4).…”

“…However, despite these advances, the involvement of Dvl in oncogenesis is largely unknown. Recently, expression of Dvl-1 protein has been found in breast cancer, cervical squamous cell carcinoma and prostate cancer [22][23][24]. Also, Dvl-3 protein is expressed in malignant mesotheliomas and in six of eight lung cancers tested (Dvl-1 and Dvl-2 proteins were undetectable in the lung cancer cases) [25,26].…”