PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews
| Autor: | Chunyan Wang, Guang-Zhe Ge, Longbao Lv, Ceshi Chen, Jian-Lin Jiao, Hou-Jun Xia, Hailin Zhang, Bao-Li He, Yuan-Xu Zhang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty 9 10-Dimethyl-1 2-benzanthracene Mammary gland DMBA Mammary Neoplasms Animal Medroxyprogesterone Acetate Biology Gene mutation Papilloma Intraductal Random Allocation chemistry.chemical_compound Mammary Glands Animal Breast cancer Intraductal papilloma medicine Animals PTEN skin and connective tissue diseases neoplasms Progesterone 7 12-Dimethylbenz[a]anthracene Carcinoma Ductal Breast PTEN Phosphohydrolase Tupaiidae GATA3 Mammary Neoplasms Experimental Estrogens medicine.disease Carcinoma Papillary Disease Models Animal medicine.anatomical_structure Receptors Estrogen Oncology chemistry Mutation Carcinogens biology.protein Female Phosphatidylinositol 3-Kinase Receptors Progesterone |
| Zdroj: | European Journal of Cancer. 50:3230-3242 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2014.10.012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect