In a recent study, researchers from Oregon State University have identified a genetic function that helps "tumor suppressor" genes to do its job better and prevent cancer.
The gene identified is known as Grp1. Ways to maintain or increase the effectiveness of Grp1-associated scaffold protein or Grasp might possibly offer an important new avenue for cancer treatment, according to scientists. The findings are published in Photochemical and Photobiological Sciences, a journal of the Royal Society of Chemistry, by researchers from OSU and Oregon Health & Science University. The work was supported by the National Institute of Environmental Health Sciences.
The researchers studied Grasp gene in the skin of mice. However, studies have shown that Grasp gene is actually expressed at the highest levels in the brain, heart and lung. This gene is also shown to play a critical role in the operation of the p53 tumor suppressor gene, the focus of much modern cancer research. This is the gene that repairs damaged DNA. In case the damage is too great, p53 gene causes the mutated cell to die before it can cause further problems leading to cancer. More than half of all known cancers including skin, esophageal, colon, pancreatic, lung, ovarian, and head and neck cancers are linked to dysfunctional p53 genetic pathways.
"DNA mutations occur constantly in our bodies just by ordinary stresses, something as simple as exposure to sunlight for a few seconds," said Mark Leid, professor of pharmacology and associate dean for research in the OSU College of Pharmacy, and one of the lead authors on this study.
"Just as constantly, the p53 gene and other tumor suppressors are activated to repair that damage," Leid said. "And in cases where the damage is too severe to be repaired, p53 will cause the apoptosis, or death of the mutated cell. Almost all of the time, when they are working right, these processes prevent the formation of cancers."
However, the activity of p53 can fail at times, according to Leid leading to the development of cancer. The current research promises to pave way for cancer therapy based on stimulating or activating p53 protein to do its job.
This study has identified the huge role that the Grasp gene plays in maintaining the proper function of p53. There could be occasions when Grasp gene does not get adequately expressed. In such cases the p53 protein that has entered the cell nucleus to either repair or destroy the cell comes back out of the nucleus before its work is finished.
"It appears that a primary function of Grasp is to form sort of a halo around the nucleus of a damaged skin cell, and act as kind of a plug to keep the p53 cell inside the nucleus until its work is done," Leid said. "A drug that could enhance Grasp function might also help enhance the p53 function, and give us a different way to keep this important tumor suppressor working the way that it is supposed to. "This could be important," he said.
"It appears that a primary function of Grasp is to form sort of a halo around the nucleus of a damaged skin cell, and act as kind of a plug to keep the p53 cell inside the nucleus until its work is done," Leid said. "A drug that could enhance Grasp function might also help enhance the p53 function, and give us a different way to keep this important tumor suppressor working the way that it is supposed to. "This could be important," he said.
The scientists created lab mice lacking Grasp gene. When the mice were reared in a perfect environment, they developed normally. However, even mild environmental stressor like UV light similar to moderate sun exposure, they began to develop cellular abnormalities much more rapidly than ordinary mice. Yet, the mutated skin cells did not die as they were expected to.
OSU experts created laboratory mice that lacked the Grasp gene, and so long as the mice were reared in a perfect environment, they developed normally. But when they were exposed to even a mild environmental stress – ultraviolet light similar to moderate sun exposure – they began to develop cellular abnormalities much more rapidly than ordinary mice. Most significantly, mutated skin cells did not die as they should have.
Most current cancer therapies related to the p53 tumor suppression process are directed toward activating the p53 protein, Leid said. A therapy directed toward improving the Grasp gene function would be a different approach toward the same goal, he said, and might improve the efficacy of treatment.
No comments:
Post a Comment