Dishevelled family proteins (DVL1, DVL2, and DVL3) are cytoplasmic mediators involved in canonical and non-canonical Wnt signaling that are important for embryonic development. Since Wnt signaling promotes cell proliferation and invasion, its increased activation is associated with cancer development as well. To get deeper insight into the behavior of Dishevelled proteins in cancer, we studied their expression in serous ovarian carcinomas [both low- (LGSC) and high-grade (HGSC)], and HGSC cell lines OVCAR5, OVCAR8, and OVSAHO. DVL protein expression in serous ovarian carcinomas tissues was analyzed using immunohistochemistry, while DVL protein and mRNA expressions in HGSC cell lines were analyzed using Western blot and quantitative real-time PCR. DVL1 protein expression was significantly higher in LGSC compared with normal ovarian tissue, while DVL3 was overexpressed in both LGSC and HGSC. DVL2 and DVL3 protein expression was higher in HGSC cell lines when compared with normal control cell line FNE1, while DVL1, DVL2, and DVL3 mRNA expression was significantly increased only in OVSAHO cell line. Survival analysis revealed no significant impact of DVL proteins on patients' outcome. Our data show an active involvement of Dishevelled family proteins in serous ovarian carcinomas. Further studies should confirm the clinical relevance of these observations.

中文翻译：

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浆液性卵巢癌中杂乱的家族蛋白：临床病理和分子研究。

杂乱的家族蛋白（DVL1，DVL2和DVL3）是参与经典和非经典Wnt信号传导的细胞质介体，对胚胎发育很重要。由于Wnt信号传导促进细胞增殖和侵袭，因此其增强的激活作用也与癌症的发展有关。为了更深入地了解Disheveled蛋白在癌症中的行为，我们研究了它们在浆液性卵巢癌[低（LGSC）和高级别（HGSC）]以及HGSC细胞系OVCAR5，OVCAR8和OVSAHO中的表达。使用免疫组织化学分析浆液性卵巢癌组织中的DVL蛋白表达，并使用Western blot和定量实时PCR分析HGSC细胞系中的DVL蛋白和mRNA表达。与正常卵巢组织相比，LGSC中DVL1蛋白的表达明显更高，而DVL3在LGSC和HGSC中均过表达。与正常对照细胞系FNE1相比，HGSC细胞系中的DVL2和DVL3蛋白表达更高，而仅在OVSAHO细胞系中DVL1，DVL2和DVL3 mRNA表达显着增加。生存分析显示DVL蛋白对患者预后没有明显影响。我们的数据显示Disheveled家族蛋白积极参与浆液性卵巢癌。进一步的研究应证实这些观察结果的临床意义。生存分析显示DVL蛋白对患者预后没有明显影响。我们的数据显示Disheveled家族蛋白积极参与浆液性卵巢癌。进一步的研究应证实这些观察结果的临床意义。生存分析表明DVL蛋白对患者预后没有明显影响。我们的数据显示Disheveled家族蛋白积极参与浆液性卵巢癌。进一步的研究应证实这些观察结果的临床意义。