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Ancient mechanism for coping with stresses also gives cancer a boost
Date:9/20/2007

metabolism and other basic cell functions. Scientists had also long noted that HSP levels increase in many cancer cells.

"The odd thing is, apparently no one thought it was that interesting," Lindquist said. Therefore, whether the stress management proteins played a causal, supportive, or inhibitory role in cancer remained an unanswered question. "On the one hand, given its prominent role in helping cells cope with stressful insults, HSF1 might promote [cancer's formation] by facilitating cellular adaptation to the malignant lifestyle," she explained. "On the other hand, given its general role in enhancing longevity, HSF1 might assist organisms in combating malignancy."

To find out, the researchers first looked to a common mouse model of skin cancer, in which the animals' are exposed to cancer-causing chemicals. Mice unable to switch on the heat-shock response were "far more resistant" to tumor formation than normal mice were under those conditions, they found. It took the mutant mice five weeks longer to develop tumors. They were less likely to develop cancer and, when they did, had fewer and smaller tumors. The HSF1-deficient mice also lived longer.

The researchers next examined mice predisposed to develop cancer due to a deficiency of the tumor suppressor p53, the most frequently mutated gene in human cancers. Again, they found, the HSF1-deficient animals lived tumor-free for dramatically longer. Indeed, even cancer-prone animals lacking just one working copy of HSF1 lived longer than normal animals did. Through studies in cultured mouse cells, they found further evidence that HSF1 supports the transformation to cancer by orchestrating a variety of basic cell functions, including proliferation, survival, protein synthesis, and glucose metabolism.

They then examined the role of HSF1 in normal and cancerous human cells, including those derived from the breast, prostate, and cervix. In every case, they found that the cancerous cel
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Contact: Nancy Wampler
nwampler@cell.com
617-386-2121
Cell Press
Source:Eurekalert

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