Mouse genetic background influences whether HrasG12V expression plus Cdkn2a knockdown causes angiosarcoma or undifferentiated pleomorphic sarcoma
| Autor: | Ana Filipa Gonçalves, Tomas Hejhal, Antonella Catalano, Ian J. Frew, Svende Pfundstein, Laura P Brandt, Joachim Albers, Peter J. Wild |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Gene knockdown angiosarcoma mouse model Biology H-Ras medicine.disease Undifferentiated Pleomorphic Sarcoma Small hairpin RNA undifferentiated pleomorphic sarcoma 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Oncology CDKN2A 030220 oncology & carcinogenesis Cancer research biology.protein medicine PTEN Angiosarcoma HRAS Sarcoma Research Paper MuLE lentivirus |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | Soft tissue sarcomas are rare mesenchymal tumours accounting for 1% of adult malignancies and are fatal in approximately one third of patients. Two of the most aggressive and lethal forms of soft tissue sarcomas are angiosarcomas and undifferentiated pleomorphic sarcomas (UPS). To examine sarcoma-relevant molecular pathways, we employed a lentiviral gene regulatory system to attempt to generate in vivo models that reflect common molecular alterations of human angiosarcoma and UPS. Mice were intraveneously injected with MuLE lentiviruses expressing combinations of shRNA against Cdkn2a, Trp53, Tsc2 and Pten with or without expression of HrasG12V , PIK3CAH1047R or Myc. The systemic injection of an ecotropic lentivirus expressing oncogenic HrasG12V together with the knockdown of Cdkn2a or Trp53 was sufficient to initiate angiosarcoma and/or UPS development, providing a flexible system to generate autochthonous mouse models of these diseases. Unexpectedly, different mouse strains developed different types of sarcoma in response to identical genetic drivers, implicating genetic background as a contributor to the genesis and spectrum of sarcomas. |
| Databáze: | OpenAIRE |
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