A recent study published in The American Journal of Pathology by Thomas Jefferson University researchers has shown that the absence of a specific sirtuin enzyme, SIRT1, can result in the formation of early prostate cancer in animal models of the disease.
Sirtuin enzymes are a class of proteins endowed with deacylase activity, and have been linked with several types of malignancies including neurodegeneration, obesity, heart disease, and cancer.
“Using genetic deletion we found that SIRT1 normally restrains prostatic intraepithelial neoplasia in animals. Therefore too little SIRT1 may be involved in the cellular processes that starts human prostate cancer,” study author Dr. Richard Pestell, M.D., Ph.D., MBA, executive Vice President of Thomas Jefferson University and Director of the Sidney Kimmel Cancer Center, said in a news release. “As we had shown that gene therapy based re expression of SIRT1 can block human prostate cancer tumor growth, and SIRT1 is an enzyme which can be targeted, this may be an important new target for prostate cancer prevention.”
In their study, titled “Loss of Sirt1 Promotes Prostatic Intraepithelial Neoplasia, Reduces Mitophagy, and Delays Park2 Translocation to Mitochondria”, the team designed a mouse model that was not able to produce SIRT1. These animals had a tendency to develop prostatic intraepithelial neoplasia (PIN), an early type of prostate cancer.
Previous studies had already demonstrated that SIRT1 was able to protect cells against damage, however, in this new study, Dr. Pestell and his team were able to show that in animal models of prostate cancer, cells which lacked this specific sirtuin experienced an accumulation of free radicals.
In a normal situation, SIRT1 activates SOD2, a mitochondrial protein that has the capacity to maintain normal levels of free-radicals. However, upon loss of SIRT1, the activity of SOD2 is compromised, leading to prostatic intraepithelial neoplasia development.
“The next step is to determine if this is also important in the development of human prostate cancer”, first author Gabriele DiSante, Ph.D., a postdoctoral fellow in the department of Cell Biology at Jefferson, added in the news release.