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New Trigger for Breast Cancer

31 January 2005 (All day)
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Cancer causer. Breast cells become cancerous when they express Env, a viral gene that contains a growth-promoting genetic sequence expressed in immune cells.

Researchers have found new support for a link between viral infection and breast cancer. A snippet of genetic code normally expressed in immune system cells can trigger the disease when its part of a virus's DNA.

The idea that a virus can cause human breast cancer has been around for nearly fifty years. Though unproven and hotly debated, the theory remains intriguing because known cancer-causing genes such as BRCA-1 explain only a percentage of human breast cancer cases, and because viruses do cause other forms of cancer in humans and animals. Genome studies show that several such viruses, including one that infects mouse mammary cells and has been linked to cancer, have something in common--a sequence of DNA similar to that found in immune system cells. The sequence, called an ITAM (immunoreceptor tyrosine-based activation motif), encodes a piece of protein that can by itself signal immune system cells to multiply and go to work.

Curious about the effect a virally-encoded ITAM might have on cells outside the immune system, immunologist John Monroe of the University of Pennsylvania and breast cancer researcher Jose Russo from the Fox Chase Cancer Center in Philadelphia expressed Env, a mouse virus gene that contains ITAM DNA, in mouse and human breast cells. The growth rate of the cells exploded, and they quickly became disorganized masses characteristic of early stage, aggressive breast cancer, the team reports in the 7 February issue of the Journal of Experimental Medicine. Because immune cells exposed to the ITAM DNA were unaffected, Monroe postulates that cells outside the immune system lack the natural inhibitors that keep ITAM growth commands in check.

The ability of the ITAM sequence to make cells cancerous represents a potential new trigger for breast cancer in humans, say the researchers, and gives further credence to the idea that viruses can cause human breast cancer. As many as 40% of human breast tumors contain ITAM sequences similar to those found in the mouse virus, they note. "Until now, ITAMs were not thought to play any role in the development of cancer," said Monroe.

This is a "very significant" study, says virologist Robert Garry of the Tulane University Health Sciences Center in New Orleans, Louisiana. He notes that these findings "fill in gaps" in our understanding of the mechanisms that cause breast cancer and may encourage some researchers to rethink their position on viruses as a trigger of the disease.

Related sites
Monroe's Lab
Viruses linked to human cancers

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