Restucci Brunella, Maiolino Paola, Martano Manuela, Esposito Giuseppe, De Filippis Daniele, Borzacchiello Giuseppe, Lo Muzio Lorenzo
Departments of Pathology and Animal Health, Faculty of Veterinary Medicine, University Federico II, Naples, Italy.
Anticancer Res. 2007 Sep-Oct;27(5A):3083-9.
Mammary tumors are a very common neoplasm in the dog and show histological features and biological behaviour similar to human mammary carcinomas. Recently, a pathway named Wnt-1, involving beta-catenin and APC protein, has emerged as an important player in many human tumor types, including mammary neoplasms.
Thirty-five samples of canine mammary tumors (10 benign and 25 malignant) were studied in order to evaluate the co-expression of beta-catenin, APC protein and E cadherin with confocal laser microscopical observation, by western blot analysis and by correlating data obtained with the histological grade of tumours.
A progressive decrease of E-cadherin together with disruption of beta-catenin expression was observed in less differentiated malignant tumors. In addition, a loss of beta-catenin membranous distribution and a cytoplasmic accumulation was often coexpressed with disrupted expression of APC protein. Western blot analysis showed a progressive increase of beta-catenin in malignant tumors, which could be the expression of disrupted /-catenin catabolism leading to cytoplasmic accumulation. In some less differentiated malignant tumors, a marked beta-catenin decrease was also observed. This feature could be linked to mutations in beta-catenin gene coding for a truncated and lighter protein.
These results may indicate the multifunctional role played by beta-catenin in canine mammary oncogenesis.
乳腺肿瘤是犬类非常常见的一种肿瘤,其组织学特征和生物学行为与人类乳腺癌相似。最近,一条涉及β-连环蛋白和APC蛋白的名为Wnt-1的信号通路,在包括乳腺肿瘤在内的许多人类肿瘤类型中成为一个重要因素。
研究了35个犬乳腺肿瘤样本(10个良性和25个恶性),通过共聚焦激光显微镜观察、蛋白质免疫印迹分析以及将所得数据与肿瘤组织学分级相关联,来评估β-连环蛋白、APC蛋白和E-钙黏蛋白的共表达情况。
在分化程度较低的恶性肿瘤中,观察到E-钙黏蛋白逐渐减少,同时β-连环蛋白表达紊乱。此外,β-连环蛋白膜分布的丧失和细胞质积累常常与APC蛋白表达紊乱共同出现。蛋白质免疫印迹分析显示恶性肿瘤中β-连环蛋白逐渐增加,这可能是β-连环蛋白分解代谢紊乱导致细胞质积累的表现。在一些分化程度较低的恶性肿瘤中,也观察到β-连环蛋白明显减少。这一特征可能与编码截短且较轻蛋白质的β-连环蛋白基因突变有关。
这些结果可能表明β-连环蛋白在犬乳腺肿瘤发生过程中发挥的多功能作用。