Introduction of oncogenes into mammary glands
            <i>in vivo</i>
            with an avian retroviral vector initiates and promotes carcinogenesis in mouse models

Du, Zhifeng; Podsypanina, Katrina; Huang, Shixia; McGrath, Amanda; Toneff, Michael J.; Bogoslovskaia, Ekaterina; Zhang, Xiaomei; Moraes, Ricardo; Fluck, Michele M.; Allred, D. Craig; Lewis, Michael T.; Varmus, Harold; Li, Yi

doi:10.1073/pnas.0608607103

Cited by 103 publications

(180 citation statements)

References 46 publications

Supporting

Mentioning

175

Contrasting

Order By: Relevance

“…After the lentivirus was injected into the mammary ducts of mice, all mice developed mammary tumors with the average latency of 12.5 days. 15 This study indicated that PyMT is very strong carcinogen capable of inducing mammary tumors with only minor amounts of lentivirus needed to transform the normal mammary epithelial cells. The PyMT oncogene encodes a membrane-bound virus protein which can activate c-Src and a number of oncogenic signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Self Cite

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 99%

“…All six ERa-negative cases (#4, 11,13,14,15,17) showed no or weak activation of ERK and STAT3. However, activation of AKT were not correlated with the ERa status in these tumors.…”

Section: Pymt Activates Oncogenic Signaling Pathways In Mammary Tumorsmentioning

confidence: 99%

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Oncogenic transformation often leads to the loss of cell-to-cell contact inhibition 18,19 and results in cells piling up on top of each other forming transformed clusters as observed in Figure 1C and D.…”

Section: Analyzing Images Of Cellular Clusters and Quantifying Reversmentioning

confidence: 99%

Validation of a High-Content Screening Assay Using Whole-Well Imaging of Transformed Phenotypes

Ramirez

Ozawa

Takagi

et al. 2011

ASSAY and Drug Development Technologies

View full text Add to dashboard Cite

Automated microscopy was introduced two decades ago and has become an integral part of the discovery process as a high-content screening platform with noticeable challenges in executing cell-based assays. It would be of interest to use it to screen for reversers of a transformed cell phenotype. In this report, we present data obtained from an optimized assay that identifies compounds that reverse a transformed phenotype induced in NIH-3T3 cells by expressing a novel oncogene, KP, resulting from fusion between platelet derived growth factor receptor alpha (PDGFRa) and kinase insert domain receptor (KDR), that was identified in human glioblastoma. Initial image acquisitions using multiple tiles per well were found to be insufficient as to accurately image and quantify the clusters; whole-well imaging, performed on the IN Cell Analyzer 2000, while still two-dimensional imaging, was found to accurately image and quantify clusters, due largely to the inherent variability of their size and well location. The resulting assay exhibited a Z ' value of 0.79 and a signal-to-noise ratio of 15, and it was validated against known effectors and shown to identify only PDGFRa inhibitors, and then tested in a pilot screen against a library of 58 known inhibitors identifying mostly PDGFRa inhibitors as reversers of the KP induced transformed phenotype. In conclusion, our optimized and validated assay using whole-well imaging is robust and sensitive in identifying compounds that reverse the transformed phenotype induced by KP with a broader applicability to other cell-based assays that are challenging in HTS against chemical and RNAi libraries.

show abstract

“…This system employs retroviral gene delivery whereby expression can be targeted to cells of mice transgenic for the avian subgroup A receptor gene (tva). This system has recently been employed successfully to introduce PyMT and ErbB2 in mammary epithelial cells of MMTV-tva transgenic mice [99]. Moreover, oncogene collaboration could be assessed by infection of MMTVtva; MMTV-Wnt bitransgenic mice with RCAS virus carrying an activated ErbB2 oncogene.…”

Section: Conditional Mouse Models Of Breast Cancermentioning

confidence: 99%

Modeling Metastatic Breast Cancer in Mice

Jonkers

Derksen

2007

J Mammary Gland Biol Neoplasia

View full text Add to dashboard Cite

Metastatic disease is the major cause of death in breast cancer patients. Patients presenting with metastases cannot be cured, and as a consequence, treatment is palliative and focuses on prolonging survival and maintaining quality of life. Numerous mouse models have been generated in which human breast cancer development and metastasis have been studied, ranging from spontaneous and carcinogen-induced models to transplantation models and genetically engineered mouse models. Here, we summarize past progress and highlight present developments in modeling breast cancer invasion and metastasis in genetically modified mice, and the impact it may have on the development of innovative anticancer therapies.

show abstract

Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models

Cited by 103 publications

References 46 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

Validation of a High-Content Screening Assay Using Whole-Well Imaging of Transformed Phenotypes

Modeling Metastatic Breast Cancer in Mice

Contact Info

Product

Resources

About