Aiding and abetting: a longevity gene also promotes cancer.

A gene that helps organisms survive damage to their cells can also shorten their lives by fostering tumors, tests on mice and human-cell lines show.

The gene, called heat-shock factor 1 (Hsf1), doesn't itself trigger cancer. Instead, it appears to help cells survive the stressful process of becoming cancerous, which involves extensive damage to DNA and the malfunctioning of many proteins.

The discovery reveals a dark side of Hsf1, which is known to promote longevity in labgrown roundworms and to protect people against the brain-cell damage of Alzheimer's and Parkinson's diseases. Some researchers are developing drugs that might ease the brain diseases by boosting Hsf1 activity.

Now it appears that hindering Hsf1 could be a new way to combat cancer.

The new study "does bring [Hsf1] forward as a possible therapeutic target" in cancer research, says team member Luke Whitesell of the Whitehead Institute for Biomedical Research in Cambridge, Mass. However, Whitesell cautions that more work is needed before scientists can develop cancer drugs that exploit this discovery.

The cancer-facilitating effects of Hsf1 may stem from its role as the ringleader of so-called heat-shock proteins. Stresses such as excessive heat, exposure to free radicals, or a lack of oxygen can damage a cell's molecular machinery. When that happens, heat-shock proteins can keep a cell healthy by either fixing or expelling damaged cellular components.

Hsf1 activates this repair system by boosting the activity of heat-shock proteins. The gene also regulates proteins involved in energy production and cell proliferation, which might also contribute to the gene's ability to aid cancer formation.

Scientists had previously observed that tumor cells often have abnormally high quantities of heat-shock proteins. White-sell and his colleagues wondered whether those proteins had a role in keeping the tumor cells alive.

The researchers tested their idea by inducing skin cancer in 29 normal mice and 23 mice engineered to lack Hsf1. The mice without Hsf1 had a significantly lower incidence of cancer than did the genetically normal group, the team reported in the Sept. 21 Cell. After 55 weeks, more than 90 percent of the Hsf1-free mice were still alive, while only about 35 percent of the normal mice had survived.

When Whitesell's team repeated the experiment on mice with a cancer-causing genetic mutation, about 75 percent of the mice without Hsf1 survived at least 90 weeks, while none of the mice with intact Hsf1 genes did.

Some cancers appear to have a similar dependence on the gene. The researchers blocked Hsf1 activity in a variety of human-cancer cells growing in the lab. In all cases, most of the cancer cells died. Healthy human cells growing in similar conditions showed no ill effects from blocking the gene's activity, reinforcing the point that Hsf1 is critical only for cells under duress.

"I thought the results were very clear," comments Stephen J. Elledge of Harvard Medical School in Boston, who wrote a commentary on the work for Cell. "This [gene] has a major role in affecting tumor formation."