Human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies

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Abstract

It has been reported that a human murine mammary tumour virus (MMTV)-like virus (HMLV), which may be an endogenous human retrovirus (HERV), occurs in the human breast cancer cell lines T47D and MCF-7 and, in 38% of human breast cancer biopsies. As the aetiology of most breast cancers remains unknown, it is important to verify these observations in differing breast cancer populations worldwide. Thus, we sought to determine the genetic relationships between HMLVs, MMTVs, and HERVs, and to investigate the association between HMLVs and breast cancer biopsies from South London, UK. Phylogenetic analyses of the env/pol region indicated that HMLVs are indistinct from MMTVs, and that MMTVS/HMLVs exhibit only low sequence homologies with HERVs. A search of the human genome confirmed that HMLVs are not endogenous. Using MMTV polymerase chain reaction (PCR) primers described previously, we amplified DNA from all cell lines except MCF-7 and from 7 of 44 (16%) breast cancer biopsies. A restriction fragment length polymorphism assay was designed to distinguish between HMLVs and MMTVs, and upon analyses, PCR amplicons appeared to be HMLVs. To confirm these findings, amplicons from the T47D cell line and from four randomly selected breast cancer patients were sequenced. Of 106 DNA sequences obtained, 103 were homologous with a short ann of human chromosome (Chr) 3 (3p13), two with Chromosome 4. and one with Chromosome 8. None of the sequences exhibited significant nucleotide homology with MMTVs, HMLVs, or with HERVs (all
Original languageEnglish
Pages (from-to)393 - 404
Number of pages12
JournalVirology
Volume318
Issue number1
DOIs
Publication statusPublished - 5 Jan 2004

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biopsy
  • Breast Neoplasms/virology
  • Cell Line, Tumor
  • Endogenous Retroviruses/classification
  • Female
  • Humans
  • Mammary Tumor Virus, Mouse/classification
  • Mice
  • Middle Aged
  • Molecular Sequence Data
  • Phylogeny
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Sequence Analysis, DNA

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