Three loci modify growth of a transgene-induced mammary tumor: Suppressionof proliferation associated with decreased microvessel density

In earlier studies it was observed that the genetic background significantl y affected the phenotype of a transgene-induced mammary tumor. Tumors arisi ng in an (I/LnJ x PyMT) F-1 hybrid background appeared earlier than in the FVB/N-TgN(MMTV-PyVT)(634Mul) parent, but accumulated less tumor mass, indic ating a net decrease in tumor growth. Quantitative genetic mapping in a bac kcross identified three loci that were associated with the decreased prolif erative capacity of the I/LnJ F-1 tumors. Molecular analysis of the tumors suggests that these loci may act by restricting the tumor's ability to recr uit microvessels. The three loci, designated Mmtg1-3, are unlinked to the a ngiogenic genes Pgf2 FLt1, Flk4, Flk1, Vegf; and Vegfc, as well as the prec ursors of the endogenous antiangiogenic molecules angiostatin and endostati n. The Mmtg loci may therefore provide novel targets for antiangiogenic the rapeutic strategies.