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Mouse Mammary Tumor-Like Virus Is Associated with p53 Nuclear Accumulation and Progesterone Receptor Positivity but not Estrogen Positivity in Human Female Breast Cancer

¹ Virology Division, Department of Microbiology, South Eastern Area Laboratory Services, The Prince of Wales Hospital, Randwick; ² School of Biochemistry and Biomedical Sciences, University of New South Wales, Sydney; and ³ School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia

Purpose: The purpose is to compare the presence of proteins with known associations with breast cancer—progesterone receptor (PgR), estrogen receptor, and p53, with the prevalence of mouse mammary tumor virus (MMTV)-like DNA sequences in human female breast cancers.

Experimental Design: A cohort of 128 Australian female breast cancers were screened for MMTV-like DNA sequences using PCR. The presence of PgR, estrogen receptor, and nuclear accumulation of p53 protein was assessed in the same samples using immunohistochemical staining.

Results: Nuclear accumulation of p53 was significantly more prevalent (P = 0.05) in archival human breast cancers containing MMTV-like DNA sequences. The presence of progesterone receptor was significantly higher in MMTV-positive than MMTV-negative breast cancers (P = 0.01). No correlation between estrogen receptor and MMTV-like DNA sequences was found.

Conclusions: MMTV causes breast cancer in mice, and hormones up-regulate expression of virus in mice mammary tissue. It is unknown if this is the case in human breast cancers shown to contain DNA of MMTV-like viruses. The positive association between MMTV-like DNA sequences and PgR indicates hormones and MMTV may play a role in human breast cancer. Mutations of the tumor suppressor gene p53 are common in human breast cancer and are associated with higher grades of cancer. The association of MMTV-like DNA sequences with higher grades of cancer, and the positive association between p53 and MMTV-like DNA sequences clearly warrant additional investigation.

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