RCAS/SCL-TVA animal model allows targeted delivery of polyoma middle T oncogene to vascular endothelial progenitors in vivo and results in hemangioma development.

摘要: Purpose: To recapitulate the generation of cancer stem cells in context an intact animal using a retroviral vector capable vivo delivery oncogenes to primitive endothelial and hematopoietic cells. Experimental Design: Targeting these progenitors was achieved transgenic mice which avian TVA receptor placed under control cell leukemia ( scl/tal-1 ) gene promoter SCL +19 enhancer. Results: Injection retrovirus encoding polyoma middle T (PyMT), oncogene that transforms cells, caused rapid lethality all SCL-TVA but not TVA(−) littermates. The infected animals exhibited hemorrhagic foci several organs. Histopathologic analysis confirmed presence hemangiomas origin PyMT-transformed Surprisingly, transformed contained readily detectable numbers TVA(+) By contrast, normal blood vessels had very few lesions suggests originally by PyMT retained characteristics. Further showed tumor activation phosphatidylinositol 3-kinase/Akt S6/mammalian target rapamycin pathways, suggesting mechanism used transform . Conclusions: We conclude this experimental system can specifically deliver vascular cause fatal neoplastic disease. This model should allow natural environment immunocompetent animal, thereby enabling recapitulation genetic alterations are responsible for initiation progression human malignancies origin.