Induction of papillary carcinoma in Chinese tree shrews by lentivirus mediated PyMT overexpression i

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  Tree shrew is an attractive experimental animal model for human breast cancer.It is important to establish a high-efficiency tree shrew breast cancer model for etiology research and drug development.Our previous studies suggest that 7,12-dimethylbenz(a)anthracene(DMBA)and medroxyprogesterone acetate(MPA)induce breast tumors in tree shrews with a low frequency(<50%)and long latency(~7-month).In this study,we tried to induce mammary tumors in tree shrew by specifically injection of lentivirus expressing the PyMT oncogene into mammary ducts.Most tree shrews developed mammary tumors with a latency of about three weeks.Papillary carcinoma is the predominant tumor type except one case of invasive ductual carcinoma.One case showed lymph node and lung metastasis.Interestingly,the expression levels of phosphorylated AKT,ERK and STAT3 are elevated only in a subset of PyMT-induced mammary tumors,but not all tumors.Finally,the growth of PyMT-induced tree shrew mammary tumors were significantly inhibited by cisplatin and epidoxorubicin,two routinely used chemotherapeutic drugs in clinic.Epidoxorubicin showed a better therapeutic effect and lower toxicity than ciaplatin in this model.Therefore,we conclude that PyMT-induced tree shrew mammary tumor model may be suitable for breast cancer research and drug development in the future due to its high efficiency and short latency.
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