TRANSCRIPTION OF HUMAN ENDOGENOUS RETROVIRAL SEQUENCES RELATED TO MOUSE MAMMARY-TUMOR VIRUS IN HUMAN BREAST AND PLACENTA - SIMILAR PATTERN IN MOST MALIGNANT AND NONMALIGNANT BREAST TISSUES

The human genome contains a large variety of sequences related to the mouse mammary tumor virus (MMTV). We have investigated the range of ex pression of human endogenous retroviral sequences (HERVs) related to M MTV (human MMTV-like; HML) as RNA in 60 breast cancers, 8 nonmalignant breast tissues, and 9 placentas. This was monitored using HML group-s pecific oligonucleotide probes in hybridizations toward PCR amplificat es of HML pol sequences and internal control. The degree of expression of five HML groups varied between individuals and between tissues. On average, all HML groups were less expressed in breast tissues than in placenta. The hybridization signals of some HML RNAs were strongly co rrelated, indicating a nonstochastic mechanism and a concerted regulat ion of their expression. The PCR product from one breast cancer (BC 6) , which gave an exceptionally high expression with probe hml-6, with a 20 times stronger signal than the rest of the cancers, was cloned and sequenced. The HML-6 transcript sequences were homogeneous in BC 6. T he most predominant clone derived from the cancer was used as a probe in Southern hybridizations. The same restriction fragments were detect ed in human breast tissues, PBMCs (peripheral blood mononuclear cells) , and breast cancer cell lines, except for one of the breast cancers a nd one of the nonmalignant breast tissues, which gave different bandin g patterns. A comparison of HML expression in normal and malignant bre ast tissue from the same individual would have been more precise than our comparison of samples from different persons. Bearing this limitat ion in mind, with a single exception, human MMTV-like sequences were n ot more actively expressed in malignant than in nonmalignant breast ti ssues. Nevertheless, an interesting diversity in their expression, esp ecially between individuals, was found.