Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China.
Department of Laboratory Animal Science, Kunming Medical University, Kunming, Yunnan 650500, China.
Eur J Cancer. 2014 Dec;50(18):3230-42. doi: 10.1016/j.ejca.2014.10.012. Epub 2014 Oct 30.
Tree shrew has increasingly become an attractive experimental animal model for human diseases, particularly for breast cancer due to spontaneous breast tumours and their close relationship to primates and by extension to humans. However, neither normal mammary glands nor breast tumours have been well characterised in the Chinese tree shrew (Tupaia belangeri chinensis). In this study, normal mammary glands from four different developmental stages and 18 spontaneous breast tumours were analysed. Haematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) showed that normal mammary gland morphology and structures of tree shrews were quite similar to those found in humans. Spontaneous breast tumours of tree shrews were identified as being intraductal papilloma, papillary carcinoma, and invasive ductal carcinoma with or without lung metastasis. To further analyse breast cancer tumours among tree shrews, 40 3-4 month-old female tree shrews were orally administrated 20 mg 7,12-dimethylbenz(a)anthracene (DMBA) or peanut oil thrice, and then, 15 of these DMBA administrated tree shrews were implanted with medroxyprogesterone acetate (MPA) pellets. DMBA was shown to induce breast tumours (12%) while the addition of MPA increased the tumour incidence (50%). Of these, three induced breast tumours were intraductal papillary carcinomas and one was invasive ductal carcinoma (IDC). The PTEN/PIK3CA (phosphatase and tensin homologue/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), but not TP53 and GATA3, genes are frequently mutated in breast tumours, and the PTEN/PIK3CA gene mutation status correlated with the expression of pAKT in tree shrew breast tumours. These results suggest that tree shrews may be a promising animal model for a subset of human breast cancers with PTEN/PIK3CA gene mutations.
树鼩日益成为人类疾病，尤其是乳腺癌的有吸引力的实验动物模型，这是因为其具有自发性乳腺肿瘤，并且与灵长类动物关系密切，进而与人类关系密切。然而，在中国树鼩（Tupaia belangeri chinensis）中，正常乳腺和乳腺肿瘤均未得到很好的描述。在这项研究中，分析了来自四个不同发育阶段的正常乳腺和 18 个自发性乳腺肿瘤。苏木精和伊红（H&E）染色和免疫组织化学（IHC）显示，树鼩的正常乳腺形态和结构与人类非常相似。树鼩的自发性乳腺肿瘤被鉴定为导管内乳头状瘤、乳头状癌和浸润性导管癌，伴有或不伴有肺转移。为了进一步分析树鼩中的乳腺癌肿瘤，对 40 只 3-4 月龄的雌性树鼩进行了 20mg 7,12-二甲基苯并蒽（DMBA）或花生油的口服给药，共 3 次，然后对其中的 15 只树鼩进行了醋酸甲地孕酮（MPA）埋植。结果表明，DMBA 诱导了乳腺肿瘤（12%），而添加 MPA 增加了肿瘤的发生率（50%）。其中，三个诱导的乳腺肿瘤为导管内乳头状癌，一个为浸润性导管癌（IDC）。PTEN/PIK3CA（磷酸酶和张力蛋白同源物/磷脂酰肌醇-4,5-二磷酸 3-激酶催化亚单位 alpha），而不是 TP53 和 GATA3，基因在乳腺癌肿瘤中经常发生突变，并且 PTEN/PIK3CA 基因突变状态与树鼩乳腺肿瘤中 pAKT 的表达相关。这些结果表明，树鼩可能是具有 PTEN/PIK3CA 基因突变的人类乳腺癌的一种有前途的动物模型。
