Altered mouse mammary tumor virus transcript synthesis in T-cell lymphoma cells

Proviral copies of mouse mammary tumor virus (MMTV) are known to be amplified in certain T-cell lymphomas. Transcription of the amplified MMTV proviruses was studied in detail in two T-cell lymphoma lines and showed the production of deletions and premature termination of env mRNAs and the premature termination of gag transcripts. EL-4 cells produce three env mRNAs, and sequence analysis of cDNAs of the two smaller transcripts revealed large deletions encompassing the 3′ half of the env gene. The deletion in at least one of the altered transcripts appeared to be produced by a splicing mechanism. T-cell lymphoma line ML of DBA/2 mice also synthesizes two smaller env transcripts, both of which result from premature termination of transcription. Both lines transcribe high levels of gag mRNAs of about 0.8 kilobases in length, terminating at the end of the region encoding MMTV phosphoprotein pp21. Restriction enzyme BamHI analysis of the amplified proviruses of EL-4 and ML cells as well as of additional non-mammary tumor cell types containing amplified MMTV proviruses suggested that the amplified proviruses were derived from exogenous viruses, or activated endogenous provirus MTV-1 in the case of DBA/2 strain tumor cells.