‘Longevity’ protein may ward off precursor to prostate cancerBy ANI
Friday, January 14, 2011
WASHINGTON - New evidence suggests that the “longevity” protein SIRT1 can inhibit the development of a known precursor to prostate cancer, prostatic intraepithelial neoplasia (PIN).
Results from the study could lead to new cancer prevention drugs that could not only block prostate cancer but promote longevity.
The study by researchers from the Kimmel Cancer Center at Jefferson and two other institutions found that deletion of the Sirt1 gene, known for its life-spanning effects, in mice resulted in PIN lesion formation associated with reduced autophagy, which is the necessary degradation of a cell’s own components and most likely essential for tumor suppression.
“And these results provide a direct link for the first time between the onset of prostate cancer and the Sirt1 gene that regulate aging,” Richard G. Pestell, Director, Kimmel Cancer Center and Chairman of Cancer Biology at Thomas Jefferson University, said.
The results suggest that the Sirt1 gene promotes autophagy and further highlight the role of the protein SIRT1 (the human homologue of the yeast Silent Information Regulator 2 (Sir2) gene) as a tumor suppressor in the prostate.
According to Pestell, “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.”
Pestell’s laboratory carried out a genome-wide microarray, pathway analysis and histology on Sirt1 positive and negative transgenic mice and littermate controls.
The team found that deletion of the Sirt1 gene in mice resulted in PIN formation; features included cellular hyperplasia, increased Ki67 staining, hyperchromatic nuclei and prominent nucleoli, as well as a reduced size in prostate. Gene expression analysis further demonstrated that loss of endogenous Sirt1 inhibited autophagy, which regulates normal gland development.
The study has been published in the issue of Cancer Research. (ANI)