Identification of a proviral structure in human breast cancer

Cancer Res. 2001 Feb 15;61(4):1754-9.

Abstract

Involvement of a virus similar to mouse mammary tumor virus (MMTV) in human breast cancer has long been postulated but never demonstrated. We have detected by PCR a 660-bp sequence similar to the env gene of MMTV but not to the known endogenous viruses, in 38% of human breast cancers examined (Wang et al., Cancer Res., 55: 5173-5179, 1995). This sequence was expressed in 66% of the env-positive tumors as detected by reverse transcription-PCR (Wang et al., Clin. Cancer Res., 4: 2565-2568, 1998). In this article we report the amplification of a whole proviral structure from each of two human breast carcinomas that were env positive. Using nested extra-long PCR and primers from specific MMTV sequences, overlapping env-long terminal repeat (LTR), LTR-gag, gag-pol, and pol-env segments were successfully amplified. The 9.9-kb provirus is 95% homologous to MMTV but only 57% to human endogenous retrovirus K10 in 3.5 kb of the gag and pol genes. The provirus displays typical features of a replication competent virus, plus the open reading frame for the superantigen and the glucocorticoid responsive element. Fluorescence in situ hybridization with a 2.7-kb env-LTR sequence of an env-positive breast cancer cell line revealed that the sequence is inserted in several chromosomes but not in chromosomes from normal breast cells. The origin of the MMTV-like sequences is uncertain. Because they are undetectable in normal tissues, because the similarity between the two isolates is high (96%), and because they maintain open reading frames, they appear to be exogenous.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / virology*
  • Cloning, Molecular
  • Endogenous Retroviruses / genetics
  • Fusion Proteins, gag-pol / genetics
  • Genes, env / genetics
  • Genes, gag / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Mammary Tumor Virus, Mouse / genetics
  • Polymerase Chain Reaction
  • Proviruses / genetics*
  • Sequence Homology, Nucleic Acid
  • Terminal Repeat Sequences
  • Tumor Cells, Cultured
  • Viral Proteins

Substances

  • Fusion Proteins, gag-pol
  • Viral Proteins
  • gene 9 protein, Rotavirus B