Mice transgenic with SV40-late-promoter-driven Polyomavirus Middle T oncogene exclusively develop hemangiomas

Xu, Qin; Chen, Wantao; Wang, Zhugang; Zheng, Jiawei; Zhang, Zhiyuan

doi:10.1007/s11248-008-9232-1

Cited by 3 publications

(3 citation statements)

References 22 publications

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“…Many studies have shown that PyMT is a key player in the growth of tumors and can cause cell death in vitro, which can lead to benign and malignant tumors in organs such as the skin, salivary gland, and mammary gland of mice [ 69 , 70 ]. Xu et al [ 71 ] made an IH animal model by microinjecting the PyMT transgenic DNA of polyomavirus into fertilized embryos, transferring them to mice that looked like they were pregnant, and observing the tumors in the newborn mice’s phenotypes and histological shapes (Fig. 3 ).…”

Section: Transviral and Genetic Modelsmentioning

confidence: 99%

Infantile hemangioma models: is the needle in a haystack?

Kong

Wang

et al. 2023

J Transl Med

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Infantile hemangioma (IH) is the most prevalent benign vascular tumor in infants, with distinct disease stages and durations. Despite the fact that the majority of IHs can regress spontaneously, a small percentage can cause disfigurement or even be fatal. The mechanisms underlying the development of IH have not been fully elucidated. Establishing stable and reliable IH models provides a standardized experimental platform for elucidating its pathogenesis, thereby facilitating the development of new drugs and the identification of effective treatments. Common IH models include the cell suspension implantation model, the viral gene transfer model, the tissue block transplantation model, and the most recent three-dimensional (3D) microtumor model. This article summarizes the research progress and clinical utility of various IH models, as well as the benefits and drawbacks of each. Researchers should select distinct IH models based on their individual research objectives to achieve their anticipated experimental objectives, thereby increasing the clinical relevance of their findings.

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Section: Transviral and Genetic Modelsmentioning

confidence: 99%

Infantile hemangioma models: is the needle in a haystack?

Kong

Wang

et al. 2023

J Transl Med

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“…Many studies have claimed to have a mouse model of hemangioma. A transgenic mouse with SV40 promoter-driven Polyomavirus Middle T gene demonstrated abnormal vascular proliferation with cavernous hemangioma-like structures in the skin, tongue, ear and gastric mucosa (Xu et al, 2009). The authors of this paper claimed that this was a model for IH; however, these tumors did not involute.…”

Section: Past Studiesmentioning

confidence: 99%

Infantile Hemangiomas: A Disease Model in the Study of Vascular Development, Aberrant Vasculogenesis and Angiogenesis

Wong¹,

Wu²

2012

Tumor Angiogenesis

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“…To investigate the etiology of this disease, we and others reported a transgenic model of hemangioma that expresses the polyoma middle T antigen (PyMT), the principal oncoprotein of the murine polyomavirus. The transgenic mice were characterized by spontaneous hemangiomas [ 3 , 4 ]. However, there are still some unresolved problems in this model that limit its application.…”

Section: Introductionmentioning

confidence: 99%

Disruption and inactivation of the PP2A complex promotes the proliferation and angiogenesis of hemangioma endothelial cells through activating AKT and ERK

Xie

Bao

et al. 2015

Oncotarget

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Hemangioma is a benign vascular neoplasm of unknown etiology. In this study, we generated an endothelial-specific PyMT gene-expressing transgenic mouse model that spontaneously develops hemangioma. Based on this transgenic model, a specific binding between PyMT and the core AC dimer of protein phosphatase 2A (PP2A) was verified in hemangioma vascular endothelial cells. The binding between PyMT and the PP2A AC dimer resulted in dissociation of the B subunit from the PP2A complex and inactivation of PP2A phosphatases, which in turn activated AKT and ERK signaling and promoted cell proliferation, migration and angiogenesis in vitro and tumorigenesis in vivo. Consistent with the in vitro findings, decreased PP2A phosphatase activity and disruption of the PP2A heterotrimeric complex were also observed in both primary transgene-positive TG(+) mouse hemangioma endothelial cells (TG(+) HEC cells) and human proliferating phase hemangioma endothelial (human HEC-P) cells, but not in transgene-negative TG(−) mouse normal vascular endothelial cells (TG(−) NEC cells) and human involuting phase hemangioma endothelial (human HEC-I) cells. Further, it was observed that in human hemangioma cells, endoglin could compete with the PP2A/A, C subunits for binding to the PP2A/B subunit, thereby resulting in dissociation of the B subunit from the PP2A complex. Treatment of Tie2/PyMT transgenic mice with the PP2A activator FTY720 significantly delayed the occurrence of hemangioma. Our data provide evidence of a previously unreported anti-proliferation and anti-angiogenesis effect of PP2A in vascular endothelial cells, and show the therapeutic value of PP2A activators in hemangioma.

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Mice transgenic with SV40-late-promoter-driven Polyomavirus Middle T oncogene exclusively develop hemangiomas

Cited by 3 publications

References 22 publications

Infantile hemangioma models: is the needle in a haystack?

Infantile hemangioma models: is the needle in a haystack?

Infantile Hemangiomas: A Disease Model in the Study of Vascular Development, Aberrant Vasculogenesis and Angiogenesis

Disruption and inactivation of the PP2A complex promotes the proliferation and angiogenesis of hemangioma endothelial cells through activating AKT and ERK

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