Jefferson Scientists Find Aging Gene Also Protects Against Prostate Cancer Development
(PHILADELPHIA) Cancer scientists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have shown that a gene that is involved in regulating aging also blocks prostate cancer cell growth. The researchers, led by Kimmel Cancer Center director Richard Pestell, M.D., Ph.D., hope the newly found connection will aid in better understanding the development of prostate cancer and lead to new drugs against the disease.
SIRT1 is a member of a family of enzymes called sirtuins that have far-reaching influence in all organisms, including roles in metabolism, gene expression and aging.
“We’ve shown that by making a prostate cancer with cells overexpressing a mutation for the androgen receptor, which is resistant to current forms of therapy, we can almost completely block the growth of these cells with SIRT1,” he says. Dr. Pestell and his team report their findings in November in the journal Molecular and Cellular Biology.
According to Dr. Pestell, prostate cancer cells can express a mutation that makes patients resistant to current forms of treatment such as hormonal therapy. Such therapy focuses on inactivating the androgen receptor by giving agents that shut off testosterone production.
“This study shows that there is potentially new opportunity for these cancer patients with drugs that regulate SIRT1,” Dr. Pestell says.
“The discovery is a true breakthrough in our field,” says Chawnshang Chang, Ph.D., George Hoyt Whipple Professor of Pathology and Laboratory Medicine and professor of urology and of biochemistry at the University of Rochester.
Dr. Pestell and his co-workers also found a single amino acid within the androgen receptor that reacts with SIRT1’s enzymatic activity and proved in the laboratory that it was key to its cancer-halting effect. The work could lead to a model for drug screening, Dr. Pestell notes.