Chen Maojian, Ou Chao, Yang Chun, Yang Weiping, Qin Qinghong, Jiang Wei, Tan Qixing, Mao Anyun, Liao Xiaoli, Ye Xinqing, Wei Changyuan
Department of Breast Surgery, The Affiliated Tumor Hospital of Guangxi Medical University.
Department of Clinical Laboratory, The Affiliated Tumor Hospital of Guangxi Medical University.
Biol Pharm Bull. 2019 Apr 1;42(4):580-585. doi: 10.1248/bpb.b18-00688. Epub 2019 Jan 24.
Chinese tree shrew, an animal exhibited closer evolutionary relationship with humans compared to rodents, is getting increasingly attentions as an appealing experimental animal model for human diseases. However, a high-efficiency and stable method to establish tree shrew breast precancerous lesions model has not been clearly elucidated. Thus, the current study aimed to explore the way of establishing breast precancerous model in tree shrew and investigate the pathologic characteristics of induced breast precancerous lesions. The results indicated that 7,12-dimethylbenz(a)anthracene (DMBA) could induce breast lesions in tree shrews. However, comparing to DMBA alone, an addition of medroxyprogesterone acetate (MPA) to DMBA critically increased the rate of induced breast lesion in tree shrews. Half of induced breast lesions were intraductal papilloma and the others were atypical ductal hyperplasia. Induced lesions showed positive expression of estrogen receptor α (ERα), progesterone receptor (PR) and cytokeratin 5/6 (CK5/6), but negative expression of human epidermal growth factor receptor-2 (Her-2). The expression of B cell lymphoma-extra large (Bcl-xl) was significantly higher and the expression of B cell lymphoma 2 associated X protein (Bax) was significantly lower in the precancerous lesions (atypical ductal hyperplasia) compared to benign tumor (intraductal papilloma). These results suggest that DMBA is able to induce breast lesions in tree shrews. Combination of DMBA and MPA may be more effective to establish breast precancerous lesion tree shrew models. Tree shrew might be a promising animal model for studying the tumorogenesis of breast cancer.
与啮齿动物相比，中国树鼩与人类的进化关系更为密切，作为一种有吸引力的人类疾病实验动物模型，它越来越受到关注。然而，尚未明确阐明一种高效、稳定的建立树鼩乳腺癌前病变模型的方法。因此，本研究旨在探索在树鼩中建立乳腺癌前模型的方法，并研究诱导的乳腺癌前病变的病理特征。结果表明，7,12-二甲基苯并(a)蒽(DMBA)可诱导树鼩乳腺病变。然而，与单独使用DMBA相比，在DMBA中添加醋酸甲羟孕酮(MPA)显著提高了树鼩乳腺病变的诱导率。诱导的乳腺病变中有一半是导管内乳头状瘤，另一半是不典型导管增生。诱导病变雌激素受体α(ERα)、孕激素受体(PR)和细胞角蛋白5/6(CK5/6)呈阳性表达，而人表皮生长因子受体2(Her-2)呈阴性表达。与良性肿瘤(导管内乳头状瘤)相比，癌前病变(不典型导管增生)中B细胞淋巴瘤-超大(Bcl-xl)的表达显著升高，而B细胞淋巴瘤2相关X蛋白(Bax)的表达显著降低。这些结果表明，DMBA能够诱导树鼩乳腺病变。DMBA和MPA联合使用可能更有效地建立树鼩乳腺癌前病变模型。树鼩可能是研究乳腺癌肿瘤发生的一种有前景的动物模型。
