A new common integration site, Int7, for Mouse Mammary Tumor virus in mouse mammary tumors identifies a gene whose product has furin-like and thrombospondin-like sequences

A novel common integration site for the mouse mammary tumor virus (MMTV) was identified (designated Int7) in five independently arising mouse mammary tumors. The insertion sites all cluster within a 1-kb region that is 2 to 3 kb 5 of the transcription initiation site of a gene, 2610028F08RIK, whose gene product contains furin-like and thrombospondin-like sequences. Expression of Int7 is normally very low or silent during various stages of mammary gland development, but MMTV integration at this site results in the activation of high steady-state levels of expression of the gene. These five tumors were also found to have two or three additional viral insertions, which in each case occurred flanking a member of either the Wnt and/or FGF gene family. Reverse transcriptase PCR results demonstrated that each of the viral insertions led to elevated expression of the presumed target flanking genes. The mouse mammary tumor virus (MMTV) induces preg-nancy-independent mammary adenocarcinomas in the Czech II strain of feral Mus musculus musculus with a predictable (20%) frequency after 15 months of age (reviewed in reference 3). These mice also develop preneoplastic hyperplastic nodules that can be transplanted as hyperplastic outgrowth lines. Fre