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Archive - Jul 18, 2015

“Guardian of the Genome” Protein (p53) Levels Decline with Age in Certain Epithelial Cells As Result of Epigenetic Changes; Increased Cancer Risk May Result

Researchers at UCLA have found that a protein that serves as a suppressor of cancer diminishes in skin and mouth epithelial cells as the human body ages. Dr. No-Hee Park, Dean of the UCLA School of Dentistry, and his research team have been studying p53, a tumor suppressor protein known as “the guardian of the genome” because of its involvement in DNA repair, cell cycle regulation, and cellular deterioration. “Looking at ways to maintain levels of p53 as one ages may provide a therapeutic clue to preventing cancer development,” said Dr. Park, who is also a Distinguished Professor in the Departments of Dentistry and Medicine at UCLA. Previous studies have shown that p53 accumulates in large quantities as connective tissue cells, called fibroblasts, age and stop dividing. It has been believed that the accumulation of p53 causes cells to stop dividing, which prevents out-of-control cells from growing into tumors. In an open-access article published online on July 1, 2015 in Aging Cell, the UCLA researchers found that in epithelial cells lining the skin and the mouth, the levels of p53 are actually reduced, rather than increased when cells age. Epithelial cells line the major cavities of the body, including most organs, such as the mouth, stomach, small intestine, kidney, and pancreas. These cells have a set level of p53 that provides protection from environmental factors and ensures the wellbeing of these cells. With less p53, older epithelial cells have a harder time maintaining the integrity of their genetic material when they encounter carcinogens, and this difficulty can allow cancer to develop. Dr.

Use of Sodium-Dependent Glucose Transporters by Pancreatic and Prostate Cancer Cells May Enable Better Diagnosis & Treatment of These Cancers

UCLA scientists have identified a new mechanism that delivers a key substance that fuels the growth of pancreatic and prostate cancer cells, a finding that offers new hope in the fight against two of the deadliest forms of the disease. Cancer cells require high amounts of the sugar glucose to survive and grow, and long-standing research has established passive glucose transporters, known as GLUTS, as the primary method the body uses to deliver glucose to tumors. But the results of a three-year study by UCLA researchers, have demonstrated that pancreatic and prostate cancer cells also utilize glucose from sodium-dependent glucose transporters known as SGLTs, specifically SGLT2 (image). The findings in the study, which were published online on July 13, 2015 in PNAS, provide the first promising evidence that positron emission tomography (PET) imaging techniques and SGLT2 inhibitors could be used to better diagnose and treat pancreatic and prostate cancers, said Dr. Ernest Wright, Professor of Physiology in the David Geffen School of Medicine at UCLA and lead author of the three-year study. The PNAS article is titled “Functional Expression of Sodium-Glucose Transporters in Cancer.” “This is exciting because it provides strong evidence that SGLT2 inhibitors, such as those currently approved by the FDA to treat diabetes, could potentially block glucose uptake and reduce tumor growth and increase survival in pancreatic and prostate cancers,” said Dr. Wright, who is also a member of the UCLA Jonsson Comprehensive Cancer Center. Dr. Wright, Dr. Jorge Barrio, Dr. Claudio Scafoglio, and colleagues first mapped the distribution of sodium-dependent glucose transporters in human cancer tumors, then measured glucose uptake in fresh tumors using a glucose analog specifically transported by SGLTs.