We have previously described a common integration site (designated int-3) for MMTV in virus-induced mouse mammary tumors. MMTV integration at this locus activates the expression of a 6.6- and 2.4-kb species of RNA. These RNA species correspond to flanking cellular genomic sequences that are located 5' and 3', respec- tively, of the integrated viral genome. We are currently analyzing cDNA recombinant clones of the 2.4-kb species of int-3 RNA. In other studies, we have shown that there is a significant difference in the frequency with which MMTV (C3H) integrates at int-l in BALB/cfC3H compared with C3H mammary tumors. Similarly, there is a significant difference in the frequency of MMTV (RIII) integration events at int-2 in BALB/cfRIII compared with RIII mammary tumors. These results suggest that the inbreeding program for high tumor incidence in C3H and RIII mouse strains has selected for host genetic mutations that affect the frequency of int gene activation. To begin to dissect at a genetic level the mutational events resulting in the development of preneoplastic and malignant mammary epithelial phenotypes, we have developed several mammary hyperplastic outgrowth lines (HOGs) in CZECHII V+ mice. These HOGs and primary mammary epithelia are currently being used as targets for retroviral vectors containing the int genes and other oncogenes.
