Intracisternal type A particle-mediated activation of the Notch4/int3 genein a mouse mammary tumor: Generation of truncated Notch4/int3 mRNAs by retroviral splicing events

The int3 oncogene was discovered as a frequent target in mouse mammary tumo r virus-induced mammary tumors and encodes the intracellular domain of a No tch-4/int3 protein. In one spontaneous mammary tumor, no. 9, that developed in a BALB/c mouse, we have found an insertion of a 1.2-kb sequence, consis ting of a 5' long terminal repeat and gag sequences of an intracisternal ty pe A particle (IAP) as well as an extra copy of the Notch4/int3 genomic seq uences containing exons 23 and 24, into the intron between exons 24 and 25 of the Notch4/int3 gene. In this tumor, unique splicing events between the IAP and the Notch4/int3 sequences generated two types of IAP-Notch4/int3 fu sion transcripts encoding two different portions of the intracellular domai n of Notch4/int3 proteins: one with a RAM domain and the other without. Int erestingly, these two proteins showed different subcellular localizations i n a mouse mammary epithelial cell line, HC-11.