Mouse c-mos Oncogene Activation is Prevented by Upstream Sequences

Although the molecularly cloned mouse c-mos oncogene locus can be efficiently activated by insertion of a retroviral long terminal repeat (LTR) 5′to its coding region, only low-frequency transformation occurs with the LTR element inserted 3′to this region. Analysis of several of the latter transformed cell lines suggested that loss of 2 kilobases (kb) of normal mouse DNA sequences preceding c-mos was required for oncogene activation. The determination of the transforming potential of deletion mutants containing only portions of this region followed by analysis of their nucleotide sequences identified a region termed upstream mouse sequence (UMS) as a cis-acting locus that prevents c-mos activation by a 3′LTR. The UMS region is ≈ 1 kb in length and is located 0.8-1.8 kb upstream from the first ATG in the open reading frame of c-mos. Insertion of UMS 5′to the v-mos coding region also prevents 3′LTR enhancement of its transforming activity, but this inhibition is position dependent and functions only when inserted between v-mos and its putative promoter. The results presented here suggest that UMS may function to regulate c-mos proto-oncogene expression and may explain the lack of detectable c-mos transcripts in normal mouse cells.