An ancient mechanism for coping with environmental stresses, including heat and toxic exposures, also helps cancerous tumors survive, reveals a new report in the Sept. 21, 2007, issue of Cell, a publication of Cell Press. The findings could lead to a new way to treat cancer and may also have implications for the treatment of neurodegenerative and other diseases, according to the researchers.
The scientists found that loss of the master controller of the "heat-shock response" dramatically limited the spontaneous formation of tumors in mice genetically predisposed to developing cancer, and those exposed to cancer-causing chemicals. Most importantly, they reported, depletion of the so-called heat-shock factor 1 (HSF1) in diverse previously established human cancer cell lines strongly impaired their growth and survival, while having little effect on normal cells.
"At a fundamental level, the ability of HSF1 to enable lethal malignancies is an unfortunate legacy of its ancient role in enhancing the survival of normal cells exposed to diverse acute and chronic stresses," said Susan Lindquist, a Howard Hughes investigator at the Whitehead Institute for Biomedical Research. "We expected it would have some effect on cancer, but we were surprised at the degree."
The heat-shock response is one of the most ancient and evolutionarily conserved protective mechanisms found in nature, the researchers said. While environmental insults provoke a variety of adaptive physiological responses to help organisms cope with specific stressors, the dramatic induction of heat-shock proteins (HSPs) is an essential unifying component of most of them.
The HSPs, which are under the control of a small family of heat-shock factors (HSFs), guard against the abnormal activity of other proteins in the face of stressors such as heat and oxygen starvation. Although less well understood, Lindquist said, HSFs also influence an array of other genes involved in cell
|Contact: Nancy Wampler|