Genetics of mouse mammary tumor virus-induced mammary tumors: Linkage of tumor induction to the gag gene

Retroviruses are believed to induce tumors by acting as insertional mutagen s that activate expression of cellular protooncogenes. Indeed, almost 90% o f mouse mammary turner virus (MMTV)-induced mammary tumors in C3H/He mice s how upregulation of Int protooncogenes. We have analyzed three different MM TV variants [MMTV(C3H), MMTV(HeJ), and a genetically engineered MMTV hybrid provirus (BP)] for tumorigenicity in mice from two distinct genetic backgr ounds. All three viruses were tumor causing in BALB/cJ mice. However. only MMTV(C3H), but not MMTV(HeJ) or HP, induced mammary tumors in C3H/He mice. All of the viruses were infectious on either background and up-regulated ex pression of Int genes in tumors they induced. Like HP, MMTV(HeJ) was found to be a genetic recombinant between endogenous Mtvl provirus and exogenous MMTV(C3H). Sequence comparison of MMTV variants linked the tumorigenicity o f MMTV(C3H) to the gag region of the retrovirus.