title: PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hou-Jun
authors.initials: HJ
authors.lastname: Xia
authors.affiliation: Department of Laboratory Animal Science, Kunming Medical University, Kunming, Yunnan 650500, China.
authors.forename: Bao-Li
authors.initials: BL
authors.lastname: He
authors.affiliation: 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 Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Hai-Lin
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; 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.
authors.forename: Guang-Zhe
authors.initials: GZ
authors.lastname: Ge
authors.affiliation: 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.
authors.forename: Yuan-Xu
authors.initials: YX
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Long-Bao
authors.initials: LB
authors.lastname: Lv
authors.affiliation: Department of Laboratory Animal Science, Kunming Medical University, Kunming, Yunnan 650500, China.
authors.forename: Jian-Lin
authors.initials: JL
authors.lastname: Jiao
authors.affiliation: 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. Electronic address: chenc@mail.kiz.ac.cn.
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D018270:Carcinoma, Ductal, Breast / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics; D004195:Disease Models, Animal; D004967:Estrogens / Q000378:metabolism; D005260:Female; D008321:Mammary Glands, Animal / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000139:chemically induced / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics*; D017258:Medroxyprogesterone Acetate; D009154:Mutation / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D018300:Papilloma, Intraductal / Q000235:genetics; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics*; D011374:Progesterone / Q000378:metabolism; D011897:Random Allocation; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D014418:Tupaiidae
chemical_list: D002273:Carcinogens; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D011374:Progesterone; D015127:9,10-Dimethyl-1,2-benzanthracene; D017258:Medroxyprogesterone Acetate; D058539:Phosphatidylinositol 3-Kinase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Animal model; Breast cancer; Gene mutation; PIK3CA; PTEN; Tree shrew