Wnt信号通路相关蛋白在TA2小鼠自发性乳腺癌生成中的作用

The role of Wnt signal pathway related proteins in the development of spontaneous breast cancer in TA2 mice

目的研究Wnt信号通路相关蛋白在TA2小鼠自发性乳腺癌生成中的作用。方法收集5例正常TA2小鼠的乳腺组织、5例自发性成瘤TA2小鼠的肿瘤组织及5例肿瘤对侧的乳腺癌前病变组织,用免疫组织化学方法检测TA2小鼠正常乳腺组织、自发性成瘤TA2小鼠乳腺癌前病变组织及肿瘤组织中Wnt1、Wnt5a、β-catenin蛋白的表达。结果1免疫组织化学检测结果显示:Wnt1、Wnt5a在小鼠正常乳腺组织中为阴性表达,在自发性成瘤小鼠乳腺癌前病变和乳腺癌组织胞质和细胞核中均有表达,且在自发性成瘤小鼠乳腺癌前病变的表达强度高于在乳腺癌组织中的表达。β-catenin在正常小鼠乳腺组织主要在细胞膜上表达,在自发性成瘤TA2小鼠乳腺癌前病变组织及肿瘤组织胞质中均有异常表达,且在肿瘤组织的表达强度高于其在癌前病变组织中的表达。2 Wnt1、Wnt5a、β-catenin在正常乳腺组、自发性成瘤小鼠乳腺癌前病变组、肿瘤组中的阳性细胞表达率分别为(4.46±3.57)%、(96.50±6.30)%、(90.00±1.17)%、(2.27±4.55)%、(96.24±6.00)%、(95.90±4.32)%、(4.78±3.57)%、(60.59±5.63)%、(84.87±2.56)%,三者在自发性成瘤小鼠乳腺癌前病变组、肿瘤组中的阳性细胞表达率与正常乳腺比较,差异有统计学意义(P<0.01)。Wnt1、Wnt5a在癌前病变组织中的阳性细胞表达率均高于肿瘤组织,Wnt1比较差异有统计学意义(P<0.05),Wnt5a比较差异无统计学意义(P>0.05)。β-catenin在癌前病变组织中的阳性细胞表达率低于肿瘤组织,差异有统计学意义(P<0.05)。结论 Wnt1、Wnt5a、β-catenin在TA2小鼠自发性乳腺癌生成过程中起促进作用。

Objective To investigate the role of Wnt signal pathway related proteins in the tumorigenesis of spontaneous breast cancer in TA2 mice. Methods Mammary glands were collected from tissues of normal 5 cases of TA2 mice. Spontaneous breast cancers and relevant mammary glands precancerous lesions were harvested from 5 cases of TA2 mice. Mammary tissue samples from normal TA2 mice, precancerous lesions and cancer tissues of spontaneous breast cancer-bearing TA2 mice were subsequently used to detect the expression of Wnt1,Wnt5a andβ-catenin via immunohistochemical staining. Results ① Results of immunohistochemical staining showed that the positive expression of Wnt1 and Wnt5 a located in cytoplasm in spontaneous breast cancers and mammary gland precancerous lesions from TA2 mice. The normal mammary glands were negative for Wnt1 and Wnt5a staining. The cytoplasm of precancerous lesions showed higher expression for Wnt1 and Wnt5a than them in the breast cancer. β-catenin in breast cancer and precancerous lesions were abnormal cytoplasmic expression. The expression level in breast cancer was higher than in the precancerous lesions. In normal mammary gland, the positive expression of β-catenin mainly located in the cytomembrane. ② The positive expression rates of Wnt1, Wnt5a and β-catenin in normal breast group,precancerous group and breast cancer group were （ 4. 46 ± 3. 57 ）%, （ 96. 50 ± 6. 30 ）%, （ 90. 00 ± 1. 17 ）%, （ 2. 27 ± 4. 55 ）%, （ 96. 24 ± 6. 00 ）%, （ 95. 90 ± 4. 32 ）%, （ 4. 78 ± 3. 57 ）%, （ 60. 59 ± 5. 63 ）%, （84. 87 ± 2. 56）%,respectively. The positive expression rates of the three in precancerous group and breast cancer group were significantly higher than those in normal breast group（P〈0. 01）. The positive expression rates of Wnt1, Wnt5a in precancerous group were higher than those in the tumor group,and the differences of Wnt1 had statistical significance （P〈0. 05） while Wnt5a did not （P〉0. 05）. Compared with breast cancer group,the precancerous group had lower positive expression rate of β-catenin and the differences also had statistical significance （ P 〈0. 05 ） . Conclusion Wnt1 , Wnt5 a and β-catenin promote the progression of spontaneous breast cancer in TA2 mice.