目的:建立一个合适的乳腺癌动物模型将在研究人类乳腺癌的发生、发展、转移等方面中发挥着越来越重要的作用。7,12-二甲基苯并蒽(7,12-dimethylbenz anthracene,DMBA)在实验中能诱导大鼠产生乳腺肿瘤。树鼩的基因的结构与人类的相似程度比啮齿类动物要高,而且树鼩的自发性乳腺癌已经有被报道,因而树鼩很有可能是研究乳腺肿瘤更合适的动物模型。因此我们想用致癌剂DMBA诱导树鼩产生乳腺肿瘤而建立树鼩的乳腺肿瘤模型。方法:在这个研究中,我们采用了十只在分娩之后失去幼崽的雌树鼩,其中一半的树鼩在腰部双侧乳房的脂肪垫注射100 mg/kg的DMBA,其余的树鼩作为对照组没有作DMBA处理。对生成的肿瘤组织进行病理切片HE染色的形态特点分析以及免疫组化化学法测定Ki-67、雌激素受体、孕酮受体、人表皮生长因子受体-2、E-钙粘蛋白、P120连环蛋白的表达。结果:通过诊断在DMBA处理的树鼩中,5分之1发展浸润性导管癌,其余发展成原位导管癌。结果还证明了诱导出来的乳腺肿瘤的形态学和病理学特征与人类的浸润性导管癌相似。结论:结果显示我们采用DMBA注射失去幼崽的雌树鼩的乳腺来诱导乳腺肿瘤是有效的,诱导出来的肿瘤组织学特征与人的乳腺癌相似,诱导的肿瘤组织表达目前人常用的乳腺癌相关分子生物学标记,并且表达情况与人的乳腺癌相似。这表明了DMBA诱导树鼩乳腺癌可以提供一个适合于研究人类乳腺癌发生、发展、转移和治疗的动物模型。
Objective: The establishment of a suitable animal model for study of human breast cancer development, metastasis and other aspects is more crucial. 7, 12-dimethylbenz anthracene (DMBA) has potential to induce experimental breast tumors in rat. Tree shrew is a more appropriate animal for disease models due to its genetic makeup similarities with human as compared with rodent and spontaneous breast cancers in tree shrews were already reported. Therefore, we attempt to induce breast tumor in trcc shrews by DMBA treatment. Methods: In the present study, ten female tree shrews lost their babies after delivery were employed and half of them received a single dose of 100 mg/kg DMBA by the lumbar bilateral mammary fatty pad injection, while the others were treated without DMBA as control. As a result of DMBA administration, one of five candidates had developed infiltrative ductal carcinoma (IDC), while others had developed into ductal carcinoma in situ, diagnosed with morphological features of pathological sections stained by H&E and immunohistochemistry to detect the expression of ki-67, estrogen receptor, progesterone receptor, human epidcrrnal growth factor receptor-2, E-cadherin, and p120-catenin. Results: The results demonstrated that induced breast tumors in tree shrews have shown similar morphological and pathological characteristics with humans IDC. Conclusion: From the results of experiment, the approach we take mammary gland injection DMBA in female tree shrew who had lost their babies after delivery is feasible. Histological features of induced tumor are similar to human mammary tumor, the induced tumor expressed molecular biology markers of human breast cancer, and the expression is similar to human mammary tumor. It is suggested that DMBA-induced mammary tumor model in tree shrews may provide a proper animal model in research of its occurrence, progression, metastasis, recurrence and treatment.