Enhanced c-Ki-ras expression associated with Friend virus integration in a bone marrow-derived mouse cell line.

We have investigated the molecular basis for a 25- to 30-fold overexpression of the c-Ki-ras oncogene in a mouse bone marrow-derived, early myeloid cell line, 416B. Southern blot hybridizations revealed that the 416B cells contain a rearranged c-Ki-ras gene in addition to an apparently normal gene. Molecular cloning and DNA sequence analyses demonstrated that the rearrangement involves the insertion of a 3.5-kilobase-pair segment of Friend virus that includes the envelope gene (env) and 3' long terminal repeat. The Friend provirus is positioned between a 5' nontranslated exon (exon phi) and the first coding exon (exon 1) of the c-Ki-ras gene in the same transcriptional orientation. Results of RNA blot analyses indicate that transcription from the rearranged gene initiates at a promoter that excludes sequences in exon phi. The data support the hypothesis that enhanced c-Ki-ras expression in the 416B cells results from integration of a Friend provirus within this gene.