Tumor Host Range Mutants of Polyoma and Their Targets

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DESCRIPTION (provided by the applicant): This project concerns the use of a 'tumor host range' (T-HR) selection procedure for isolation of host range mutants of Polyoma virus. The procedure involves screening and selection of virus mutants for their ability to grow on non-polyoma transformed or tumor-derived cells and inability to grow in normal primary mouse cells. The procedure is coupled to the yeast two hybrid system using wild type virus T antigen sequences as bait to screen mouse embryo cDNA libraries. Absence of interaction of target cDNAs with the mutant bait is taken as an indication of a physiologically relevant target in virus replication or transformation. The procedure is viewed as a possible way to uncover new tumor suppressor genes or other factors with which the virus must interact in normal cells in order to grow and which are altered or missing in cancer cells. We will use results from a partially characterized T-HR mutant and its putative tumor suppressor gene target to produce a mouse model of ovarian carcinoma.