Can a Retrovirus Cause Breast Cancer?

A virus that made the human genome its permanent residence long ago may be an important cause of breast cancer, if a study presented last week at a virology conference in Sydney, Australia, is correct. Researchers say they found a piece of the virus--which resembles a known breast cancer-causing virus in mice--in a high percentage of cancerous breast tissue samples. If confirmed, and if a link can be made between the presence of the virus and cancer development, the finding may help doctors predict who's at high risk for the disease.

In recent years, scientists have identified two genes that, when mutated, can cause breast cancer, but these can't account for the large majority of cases. As early as the 1940s, however, virologists stumbled across a virus that causes mammary, or breast, tumors in mice. The virus, called mouse mammary tumor virus (MMTV), is a so-called retrovirus, a type of virus that can paste its genome into the chromosomes of infected hosts. If the viral genome lands near one of the cell's many oncogenes, it may cause that gene to become abnormally active, thus leading to uncontrolled cell division and ultimately to cancer.

The discovery of MMTV set off a hunt for a similar virus in human breast cancers. But while several researchers picked up at least indirect signs that such a virus might be present there, a clearcut identification was hampered by the fact that the human genome carries thousands of so-called "human endogenous retrovirus elements," mostly harmless remnants of ancestral human retroviruses that found a permanent place in our chromosomes long ago. "This made finding an 'HMTV' like looking for a needle in a haystack," says virologist Robert Garry of Tulane University in New Orleans.

Garry and his colleagues decided to take another look. They used the highly sensitive polymerase chain reaction (PCR) to search in human breast cancer samples for an MMTV gene, known as env. They chose this one because its sequence diverges the most from that of the comparable gene in the endogenous retroviruses to make sure that any sequence they picked up was in fact from an MMTV-related gene. And the researchers found such a sequence in more than 85% of 30 breast cancer samples. To their surprise, however, they also found it in about 30% of breast tissue samples and other organs from healthy individuals. To Garry this suggests that HMTV is an intact retrovirus that inserted itself into the human genome relatively recently and is likely passed from parent to child through the germline.

Currently, however, the finding raises more questions than it answers. In 1995, for example, a team led by molecular virologist Beatriz Pogo of the Mount Sinai School of Medicine in New York City also found hints of an MMTV-like virus in human breast cancer tissue. But Pogo's team almost never found signs of the virus in healthy tissue or in other organs--which led them to believe that HMTV was not part of the genome but an infectious agent. And in any event, simply detecting signs of a virus in cancerous tissue doesn't necessarily mean that it plays a causative role. One way to learn more, says Alan Storey, a cancer virus expert at the Imperial Cancer Research Fund in London, may be to check whether virus-infected cells in culture become cancerous. In the meantime, Storey says, the new results "will clearly stimulate a lot of research" into the virus-breast cancer connection.

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