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*

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Abstract
The human genome contains a large variety of sequences related to the mouse mammary tumor virus (MMTV). We have investigated the range of expression of human endogenous retroviral sequences (HERVs) related to MMTV (human MMTV-like; HML) as RNA in 60 breast cancers, 8 nonmalignant breast tissues, and 9 placentas. This was monitored using HML group-specific oligonucleotide probes in hybridizations toward PCR amplificates 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 correlated, indicating a nonstochastic mechanism and a concerted regulation 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. The most predominant clone derived from the cancer was used as a probe in Southern hybridizations. The same restriction fragments were detected in human breast tissues, PBMCs (peripheral blood mononuclear cells), and breast cancer cell lines, except for one of the breast cancers and one of the nonmalignant breast tissues, which gave different banding patterns. A comparison of HML expression in normal and malignant breast tissue from the same individual would have been more precise than our comparison of samples from different persons. Bearing this limitation in mind, with a single exception, human MMTV-like sequences were not more actively expressed in malignant than in nonmalignant breast tissues. Nevertheless, an interesting diversity in their expression, especially between individuals, was found.