Murine mammary tumor viruses (MuMTVs) exist both as milk-transmitted exogenous and genetically-transmitted endogenous viruses. We are studying the regulation of endogenous MuMTV gene expression in various mouse strains and its effect on the emergence of mammary tumors. We have found that MuMTV expression is blocked at the transcriptional level in the BALB/c lactating mammary glands (LMG), whereas in C57BLLMG the block is at the translational level. Two endogenous MuMTV proviruses of these strains appear to have similar structure and may be integrated at very similar if not identical sites. An undetected structural difference may be responsible for the divergence of regulation observed. Using recombinant DNA clones, a detailed structural analysis and comparison will be carried out on MuMTV proviruses of BALB/c and C57BL mice, as well as their flanking host sequences. Cloned proviruses from these strains will be introduced into cultured cells by transfection and the mode of regulation over their expression will be monitored. In vitro recombination experiments will be carried out to identify structural elements involved in the regulation. Hormonal stimulation by pituitary isografts in C57BL and BALB/c mice will be used to study its effects on various aspects of endogeneous MuMTV gene expression and its relationship to mammary tumorigenesis. Explanations for the gene expression and its relationship to mammary tumorigenesis. Explanations for the genetic differences in susceptibility and resitance to mammary tumorigenesis by MuMTV will be sought using a combination of molecular biological and genetic approaches. Possible differences in preferred integration sites for MuMTV will be examined as a basis for this genetic variability. These studies will be also utilize recombinant inbred strains (CXBs) derived from the susceptibe (BALB/c) and resistant (C57BL/6) progenitor strains.
