The list of aging-associated proteins known to be involved in cancer is growing longer, according to research by investigators at Vanderbilt-Ingram Cancer Center and the National Institutes of Health (NIH).
The new study, published Oct. 17 in Cancer Cell, identifies the protein SIRT2 as a tumor suppressor linked to gender-specific tumor development in mice. Along with two other "sirtuin" proteins previously linked to cancer, the new finding suggests the existence of a rare "family" of tumor suppressors.
Cancer is primarily a disease of aging, with the majority of cancer cases occurring in people over 50. However, the biological processes that underlie this association are not clear.
In the late-1990s, sirtuins were linked to extended lifespan observed in several species maintained on a calorically restricted diet. These nutrient-sensing proteins seemed to defend against aging-related cellular damage.
"The single most important prognostic factor in cancer is increasing age," said Gius, a professor of Radiation Oncology and associate professor of Cancer Biology at Vanderbilt-Ingram. "It seems logical that the genes that play a role in aging or perhaps better stated, anti-aging would be connected to cancer."
While at the NIH's National Cancer Institute, Gius and colleagues found that when they eliminated SIRT3 a sirtuin localized in the mitochondria, the cellular "power plants" the mice developed ER/PR positive breast tumors, the most common type of breast cancer in postmenopausal women.
In the new study, Gius' lab working with senior author Chu-Xia Deng, Ph.D., and colleagues at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases investigated the physiological functions of SIRT2 by eliminating the protein in cultured cells and in mice.
They found that SIRT2-deficient mice developed tumors in multiple tissues and, strangely, male mice and female mice developed tumors in different tissues. Lack
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Vanderbilt University Medical Center