Increased concentration of an indigenous proviral mouse mammary tumor virus long terminal repeat-containing transcript is associated with neoplastic transformation of mammary epithelium in C3H/Sm mice

Abstract

Increased amounts of mouse mammary tumor virus (MMTV) proviral transcripts were found in RNA dot blots from MMTV-negative, C3H/Sm mouse mammary tumors which arose spontaneously or were induced by hormonal or chemical carcinogens or both. Other dot blots probed with a long terminal repeat (LTR) probe showed that LTR (MMTV)-containing transcripts were disproportionately represented in these tumor RNAs. Different segments of the MMTV genome were used in sequential hybridizations to Northern blots to determine relative sequence content and size of MMTV transcripts in transformed mammary tissues, as compared with those in lactating mammary glands. Increased amounts of 4.4-kilobase env and 8.1-kilobase genomic MMTV transcripts were detected with an env probe in many of the tumor RNAs examined. Hybridization of the same Northern blots containing tumor RNAs with an LTR probe revealed a 2.2-kilobase transcript which was prominent in RNAs from chemically-induced, hormonally-induced, and spontaneous mammary tumors relative to those from lactating mammary glands. The LTR-containing transcript did not possess significant homology to either env or gag-pol probes. This distinctive, transformation-enhanced, 2.2-kilobase transcript may contain mouse cellular sequences in addition to LTR sequences or it may represent the message for a nonstructural viral protein encoded within the LTR open reading frame of one or more of the four C3H/Sm MMTV proviral genes.