Mouse Mammary Tumor Virus: New Tumor Virus or Just a Rumor Virus?

Abstract

W hen German microbiologist Harald zur Hausen, M.D., D.Sc., hypothesized in 1974 that human papillomavirus (HPV) played a central role in causing cervical cancer, few took him seriously. But in 1983 he discovered HPV-16, and a year later, HPV-18 in tumors of cervical cancer patients — findings that led eventually to the first preventive cancer vaccine and, for zur Hausen, last year’s Nobel prize for medicine. Spurred by the clinical success of HPV research and the discovery of additional viruses implicated in cancer, scientists continue to hunt for other cancer-causing viruses. One leading contender, the mouse mammary tumor virus (MMTV), is a retrovirus that causes breast cancer in mice. Having found molecular evidence of its presence in human breast tumors, researchers are now investigating a possible causal link. “Among ‘rumor viruses, ’ perhaps the strongest case exists for MMTV in breast cancer,” said David Griffi ths, Ph.D., of Scotland’s Moredun Research Institute in Penicuik. Currently 15% – 25% of cancers are virally linked, with six viruses considered cofactors in or causes of human cancer: HPV in cervical cancer, hepatitis B and C in liver cancer, Epstein – Barr virus in Burkitt lymphoma and nasopharyngeal cancer, human T-cell lymphotropic virus type 1 in adult T-cell leukemia virus, and human herpesvirus 8 in Kaposi sarcoma. In addition to MMTV, other candidate viruses include simian virus 40 in mesothelioma, brain cancer, and lymphoma; cytomegalovirus in glioma; bovine leukemia virus in breast cancer and leukemia; Epstein – Barr virus in breast cancer; HPV in breast and prostate cancer; and xenotropic murine leukemia – related virus in prostate cancer. Proving a causal link is diffi cult and time consuming ( see JNCI News, 2004;96:256 – 7), and the MMTV hypothesis has gone in and out of favor over the last few decades. “In 1964, the NCI established its virus – cancer program, which focused on retroviruses after the discovery of [bovine leukemia virus] and other animal viruses, but 12 – 13 years of studies yielded nothing defi nitive,” said Gertrude Buehring, Ph.D., associate professor of virology at the University of California, Berkeley. “By the early 1980s, most everyone thought that the book was closed,” she said. In addition, the discovery of human immunodefi ciency virus in the mid-1980s diverted funding from MMTV research, according to Walter Gunzburg, Ph.D., professor of virology at the Veterinary University of Vienna. The NCI is not currently funding internal research of MMTV or other rumor viruses, but it does support external research on proven virus – cancer connections.