Formation of Prostate Cancer Precursor Blocked by "Longevity" Gene

Mice genetically engineered to lack the "longevity" gene SIRT1 demonstrated decreased levels of cellular autophagy, which resulted in the formation of precancerous lesions known as prostatic intraepithelial neoplasia (PIN). SIRT1 is an enzyme that deacetylates proteins that contribute to cellular regulation (reaction to stressors, longevity).

Autophagy is required for the degradation of damaged organelles and long-lived proteins, as well as for the development of glands such as the breast and prostate. To probe the relationship between autophagy and PIN development investigators at Thomas Jefferson University (Philadelphia, PA, USA) expanded upon previous tissue culture studies on SIRT1 by genetically engineering lines of mice either to lack or to overexpress the gene.

They reported in the December 28, 2010, online edition of the journal Cancer Research that homozygous deletion of the SIRT1 gene in mice resulted in development of PIN associated with reduced autophagy. Genome-wide gene expression analysis of prostates from mice lacking Sirt1 demonstrated that endogenous SIRT1 repressed androgen responsive gene expression and induced autophagy in the prostate.

"Prostate cancer is one of the malignancies that has a very direct relationship to aging," said senior author Dr. Richard G. Pestell, professor of cancer biology at Thomas Jefferson University. "And these results provide a direct link for the first time between the onset of prostate cancer and the SIRT1 gene that regulate aging. If you inactivate this gene, then you get the prostate cancer precursor, known as PIN. So it tells you that this "longevity" gene is normally blocking prostate cancer."

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