PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews

Xia, Houjun; He, Bao-Li; Wang, Chunyan; Zhang, Hailin; Ge, Guangzhe; Zhang, Yuanxu; Lv, Lei; Jiao, Jianlin; Chen, Ceshi

doi:10.1016/j.ejca.2014.10.012

Cited by 22 publications

(40 citation statements)

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“…4 The first spontaneous tree shrew breast cancer was reported in 1966, 5 and several of our studies have characterized a large number of spontaneous tree shrew breast cancers. 4,6 Furthermore, we demonstrated that 7,12-dimethylbenz(a)anthracene (DMBA) plus medroxyprogesterone acetate (MPA) successfully induced tree shrew breast cancer. 4 Our earlier findings make an interesting case for increased use of tree shrew models of breast cancer, but there are several drawbacks, for example, the long latency of breast tumor development (6-7 months) that varies among different animals, the fact that the tumor incidence itself is rather low (<50%), and that the induced breast tumors are in low grade and no metastasis.…”

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confidence: 87%

Generation and characterization of a breast carcinoma model by PyMT overexpression in mammary epithelial cells of tree shrew, an animal close to primates in evolution

Xia

et al. 2015

Intl Journal of Cancer

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The tree shrew is becoming an attractive experimental animal model for human breast cancer owing to a closer relationship to primates/humans than rodents. Tree shrews are superior to classical primates because tree shrew are easier to manipulate, maintain and propagate. It is required to establish a high-efficiency tree shrew breast cancer model for etiological research and drug assessment. 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), making these methods less than ideal. We induced mammary tumors in tree shrew (Tupaia belangeri chinensis) by injection of lentivirus expressing the PyMT oncogene into mammary ducts of 22 animals. Most tree shrews developed mammary tumors with a latency of about three weeks, and by 7 weeks all injected tree shrews had developed mammary tumors. Among these, papillary carcinoma is the predominant tumor type. One case showed lymph node and lung metastasis. Interestingly, the expression levels of phosphorylated AKT, ERK and STAT3 were elevated in 41-68% of PyMT-induced mammary tumors, but not all tumors. Finally, we observed that the growth of PyMT-induced tree shrew mammary tumors was significantly inhibited by Cisplatin and Epidoxorubicin. PyMT-induced tree shrew mammary tumor model may be suitable for further breast cancer research and drug development, due to its high efficiency and short latency.Breast cancer remains the most common disease in women worldwide, with some 1.7 million new cases and 500,000 deaths reported each year, the bulk of both being in developing countries.1 While total survival rates averaged across all types of breast cancer can be as high as 80% in some developed countries, in less developed areas these rates drop to <40%, primarily due to a lack of comprehensive early diagnostics paired with a dearth of cost-effective treatments. 2These lop-sided statistics-wherein the areas with the most cases have the worst outcomes and least access to treatments-highlight the importance of ongoing efforts to refine the tools for studying breast cancer and to develop more effective preventive and therapeutic treatments, especially the growing use of animal models. To date, rodents-especially transgenic mice and ratsremain the most prevalent animal models for breast cancer, largely due to size, cost efficiency and litter sizes. Unfortunately, development of anti-cancer treatments in these models suffers from poor translation to humans, with many treatments working in the rodent models but failing in human clinical trials. Though there are many potential explanations for this

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confidence: 87%

Generation and characterization of a breast carcinoma model by PyMT overexpression in mammary epithelial cells of tree shrew, an animal close to primates in evolution

Xia

et al. 2015

Intl Journal of Cancer

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“…For the induced tree shrew model of disease, surgical and/or chemical approaches are used to induce the onset of disease symptoms in the context of similar phenotypes, similar pathological mechanism, and similar clinical efficacy (McGonigle & Ruggeri, 2014; Yao et al, 2015). Hitherto, the tree shrew has been reported to be used successfully as an animal model for a variety of diseases, such as breast cancer (Ge et al, 2016; Xia et al, 2014), alcohol-induced (Xing et al, 2015) or non-alcoholic fatty liver diseases (Zhang et al, 2015, 2016), hepatitis B virus (HBV) infection (Su et al, 1987; Walter et al, 1996; Yan et al, 1996), hepatitis C virus (HCV) infection (Amako et al, 2010; Xu et al, 2007; Zhao et al, 2002), and herpes simplex virus type 1 (HSV-1) infection (Darai et al, 1978; Li et al, 2016), to name a few, albeit some results need further studies to elucidate the underlying mechanism. In previous review papers, there are ample descriptions and literature surveys of the tree shrew disease models (Cao et al, 2003; Xu et al, 2013b).…”

Section: Tree Shrews As Models For Studying Fundamental Biological Fumentioning

confidence: 99%

“…The tree shrew has a similar mammary gland to that of the human based on the morphology and structure (Xia et al, 2014) and this has provided the basis for creating a model of breast cancer. The description of spontaneous breast cancer in the tree shrew dates back to the 1960s when it was reported by Elliot and coworkers (Elliot et al, 1966), that a breast cancer was found in a female tree shrew ( Tupaia glis ) belonging to a different species within the genus Tupaia .…”

Section: Tree Shrews As Models For Studying Fundamental Biological Fumentioning

confidence: 99%

创制动物模型,为何不用树鼩呢?

姚永刚¹,

Yao²

2017

Zool. Res.

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The Chinese tree shrew (Tupaia belangeri chinensis), a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitable for use as an experimental animal. There have been many studies using the tree shrew (Tupaia belangeri) aimed at increasing our understanding of fundamental biological mechanisms and for the modeling of human diseases and therapeutic responses. The recent release of a publicly available annotated genome sequence of the Chinese tree shrew and its genome database () has offered a solid base from which it is possible to elucidate the basic biological properties and create animal models using this species. The extensive characterization of key factors and signaling pathways in the immune and nervous systems has shown that tree shrews possess both conserved and unique features relative to primates. Hitherto, the tree shrew has been successfully used to create animal models for myopia, depression, breast cancer, alcohol-induced or non-alcoholic fatty liver diseases, herpes simplex virus type 1 (HSV-1) and hepatitis C virus (HCV) infections, to name a few. The recent successful genetic manipulation of the tree shrew has opened a new avenue for the wider usage of this animal in biomedical research. In this opinion paper, I attempt to summarize the recent research advances that have used the Chinese tree shrew, with a focus on the new knowledge obtained by using the biological properties identified using the tree shrew genome, a proposal for the genome-based approach for creating animal models, and the genetic manipulation of the tree shrew. With more studies using this species and the application of cutting-edge gene editing techniques, the tree shrew will continue to be under the spot light as a viable animal model for investigating the basis of many different human diseases.

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“…In recent years, tree shrews have gained increasing attention due to their great potential as an experimental animal model of human diseases [39, 40], such as myopia [41], diabetes [42, 43], depression [44, 45], fatty liver disease [46], viral infection [47–49], hepatocellular carcinoma [50] and breast cancer [51–53]. Whole genome sequencing results demonstrated that the tree shrew lineage has a relatively closer relationship to primates than rodents [54].…”

Section: Introductionmentioning

confidence: 99%

Characterization and phylogenetic analysis of Krüppel-like transcription factor (KLF) gene family in tree shrews (Tupaia belangeri chinensis)

Shao

Liu

et al. 2016

Oncotarget

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Krüppel-like factors (KLFs) are a family of zinc finger transcription factors regulating embryonic development and diseases. The phylogenetics of KLFs has not been studied in tree shrews, an animal lineage with a closer relationship to primates than rodents. Here, we identified 17 KLFs from Chinese tree shrew (Tupaia belangeri chinensis). KLF proteins are highly conserved among humans, monkeys, rats, mice and tree shrews compared to zebrafish and chickens. The CtBP binding site, Sin3A binding site and nuclear localization signals are largely conserved between tree shrews and human beings. Tupaia belangeri (Tb) KLF5 contains several conserved post-transcriptional modification motifs. Moreover, the mRNA and protein expression patterns of multiple tbKLFs are tissue-specific. TbKLF5, like hKLF5, significantly promotes NIH3T3 cell proliferation in vitro. These results provide insight for future studies regarding the structure and function of the tbKLF gene family.

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PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7,12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews

Cited by 22 publications

References 52 publications

Generation and characterization of a breast carcinoma model by PyMT overexpression in mammary epithelial cells of tree shrew, an animal close to primates in evolution

Generation and characterization of a breast carcinoma model by PyMT overexpression in mammary epithelial cells of tree shrew, an animal close to primates in evolution

创制动物模型,为何不用树鼩呢?

Characterization and phylogenetic analysis of Krüppel-like transcription factor (KLF) gene family in tree shrews (Tupaia belangeri chinensis)

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