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Publication : Oncogenic HrasG12V expression plus knockdown of Cdkn2a using ecotropic lentiviral vectors induces high-grade endometrial stromal sarcoma.

First Author  Brandt LP Year  2017
Journal  PLoS One Volume  12
Issue  10 Pages  e0186102
PubMed ID  28982163 Mgi Jnum  J:247216
Mgi Id  MGI:5920095 Doi  10.1371/journal.pone.0186102
Citation  Brandt LP, et al. (2017) Oncogenic HrasG12V expression plus knockdown of Cdkn2a using ecotropic lentiviral vectors induces high-grade endometrial stromal sarcoma. PLoS One 12(10):e0186102
abstractText  The uterine corpus represents the most common site for tumour development in the female genital system. Uterine neoplasms are categorised as epithelial, mesenchymal, mixed epithelial-mesenchymal or trophoblastic tumours. In this study we employed a mouse genetic approach using the MuLE lentiviral gene regulatory system to functionally test the ability of ecotropic lentiviruses to model epithelial and mesenchymal uterine malignancies ex vivo and in vivo. We discovered that MuLE lentiviruses efficiently infect uterine stromal cells but not endometrial epithelial cells when injected into the uterus of cycling, pseudopregnant or ovarectomized mice. Consistent with this cellular infection spectrum, we show that intra-uterine injection of ecotropic MuLE viruses expressing oncogenic HrasG12V together with knockdown of Cdkn2a induce high-grade endometrial stromal sarcomas. These findings establish this approach as an efficient method of generating autochthonous mouse models of uterine sarcomas and in general for performing genetic manipulations of uterine stromal cells in vivo.
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