Generation Of A Breast Carcinoma Tree Shrew Model

Breast cancer is among the most prevalent forms of cancer among women, affecting some one in eight women worldwide. Thus, elucidating the underlying mechanisms that fuel the initiation and progression of breast cancer is very important to prevent and treat this kind of cancer in women. Meanwhile, the animal models are playing more and more important roles in this process. However, rodent animals, such as mice and rats, are significantly different from human beings in terms of both biology and the type of breast cancers. So, many anti-cancer drugs failed in human, clinical trials even if they worked effectively in rodent models. According to this, it is urgent to develop novel and effective brease cancer animal models. Because of its proximity to humans via phylogenomic analysis, tree shrews have the great potential to be applied into biomedical research especial tumor biology research. According to this, we try to use tree shrews to establish breast cancer animal models.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. Moreover, we collected many spontaneous breast cancer samples of tree shrews. The pathological examinaion results showed that many of these samples were papillary carcinomas.