Abstract
The Replication-Competent Avian Sarcoma-leukosis virus long-terminal repeat with splice acceptor (RCAS)-Tumor Virus A (TVA) gene delivery system has been created based on the fact that avian sarcoma leukosis virus subgroup A only infects cells expressing its receptor, TVA. This system has been successfully applied to create various mouse models for human cancers. Here we briefly discuss the advantages and the potential caveats of using this RCAS-TVA gene delivery system in cancer research. We also introduce and discuss how our newly designed RCAS-based gene delivery system (RCI-Oncogene, for RCAS-Cre-IRES-Oncogene) allows concise and efficient manipulation of gene expression in tumors in vivo, and how this system can be used to rapidly study the biological function of gene(s) and/or the collaborative actions of multiple genes in regulating tumor initiation, progression and/or metastasis.
Highlights
Series of studies focusing on mammary tumors have provided an excellent example for utilizing the spatial and temporal gene expression offered by the RCAS-Tumor Virus A (TVA) system[4, 7, 9, 10, 11, 12]
To target mammary gland, MMTV-tva transgenic mouse line has been created with a “patchy” expression pattern of TVA in the mammary luminal epithelium[4]
By intraductal injection of the RCAS-constitutively activated version of ErbB2/HER2/Neu (caErbB2) viruses into MMTV-tva mice 4-7 days before mating, this RCAS-TVA system was used to study the mechanisms underlying tumorigenesis of the pregnancy-associated breast cancers (PABCs), which are diagnosed during pregnancy, or within 5 years after parturition, in human[10]
Summary
Avian sarcoma leukosis virus subgroup A (ASLVA) only infects cells expressing its receptor, tumor virus A (TVA). The replicationcompetent ASLV long-terminal repeat (LTR) with splice acceptor (RCAS)-TVA gene delivery system was developed For this purpose, several genetically modified mouse lines expressing TVA in various specific cell types or tissues have been generated, including those targeting TVA expression in all tissues (β-actin promoter)[1], epithelium (Keratin 19 promoter)[2], Hepatocytes (Albumin promoter)[3], mammary gland epithelium (MMTV promoter)[4], endothelial cells (TIE2 promoter)[5], and skeletal and cardiac smooth muscle cells (alpha-sk-actin promoter)[6], etc. Efforts have been made to target TVA expression in cells with activation of a specific pathway, such as the TOPtva transgenic model expressing TVA driven by the Wnt-responsive TOP promoter[7] These TVAexpressing mouse lines are susceptible to infection by RCAS viruses for virus-mediated gene. We will introduce our newly designed gene delivery system that allows concisely and efficiently studying the biological function of gene(s) in tumors in vivo
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