Genetic function discovered that could offer new avenue to cancer therapies

February 3, 2014, Oregon State University

Researchers at Oregon State University have discovered a genetic function that helps one of the most important "tumor suppressor" genes to do its job and prevent cancer.

Finding ways to maintain or increase the effectiveness of this gene – called Grp1-associated scaffold protein, or Grasp – could offer an important new avenue for human cancer therapies, scientists said.

The findings were just 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 Grasp gene was studied in the skin of mice in this research, but is actually expressed at the highest levels in the brain, heart and lung, studies have shown. It appears to play a fundamental role in the operation of the p53 tumor suppressor gene, which is a focus of much modern .

The p53 gene is involved in repair of DNA damage and, if the damage is too great, causing a mutated cell to die before it can cause further problems, up to and including cancer. Dysfunction of p53 genetic pathways have been linked to more than half of all known cancers - particularly skin, esophageal, colon, pancreatic, lung, ovarian, and head and neck cancers.

"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 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."

But the activity and function of p53 can sometimes decline or fail, Leid said, and allow development of cancer. Promising approaches to cancer therapy are now based on activating or stimulating the to do its job.

The new study has found that the Grasp gene is significantly involved in maintaining the proper function of p53. When "Grasp" is not being adequately expressed, 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 working the way that it is supposed to.

"This could be important," he said.

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.

In normal mice, the same moderate light exposure caused a rapid increase in expression of the Grasp gene, allowing the p53 protein to stay in the nucleus and normal protective mechanisms to do their work.

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.

Explore further: New study shows promise for preventing therapy resistance in tumor cells

More information: rp1-associated scaffold protein regulates skin homeostasis after ultraviolet irradiation, pubs.rsc.org/en/content/articl … p50351h#!divAbstract

Related Stories

New study shows promise for preventing therapy resistance in tumor cells

January 9, 2014
A new study led by University of Kentucky researchers suggests that activating the tumor suppressor p53 in normal cells causes them to secrete Par-4, another potent tumor suppressor protein that induces cell death in cancer ...

Research reveals cancer-suppressing protein 'multitasks'

May 9, 2013
The understanding of how a powerful protein called p53 protects against cancer development has been upended by a discovery by Walter and Eliza Hall Institute researchers.

New RNA interference technique finds seven genes for head and neck cancer

January 24, 2014
(Medical Xpress)—In the hunt for genetic mutations that cause cancer, there is a lot of white noise. So although genetic sequencing has identified hundreds of genetic alterations linked to tumors, it's still an enormous ...

Deficiency in p53 anti-tumor protein delays DNA repair after radiation

April 23, 2013
Researchers at Moffitt Cancer Center have found that a deficiency in an important anti-tumor protein, p53, can slow or delay DNA repair after radiation treatment. They suggest that this is because p53 regulates the expression ...

Biologists ID new cancer weakness

November 14, 2013
About half of all cancer patients have a mutation in a gene called p53, which allows tumors to survive and continue growing even after chemotherapy severely damages their DNA.

Scientists detail critical role of gene in many lung cancer cases

August 29, 2013
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have shown that a well-known cancer-causing gene implicated in a number of malignancies plays a far more critical role in non-small cell lung cancer, ...

Recommended for you

Scientists block the siren call of two aggressive cancers

January 23, 2018
Aggressive cancers like glioblastoma and metastatic breast cancer have in common a siren call that beckons the bone marrow to send along whatever the tumors need to survive and thrive.

Boosting cancer therapy with cross-dressed immune cells

January 22, 2018
Researchers at EPFL have created artificial molecules that can help the immune system to recognize and attack cancer tumors. The study is published in Nature Methods.

Workouts may boost life span after breast cancer

January 22, 2018
(HealthDay)—Longer survival after breast cancer may be as simple as staying fit, new research shows.

Cancer patients who tell their life story find more peace, less depression

January 22, 2018
Fifteen years ago, University of Wisconsin–Madison researcher Meg Wise began interviewing cancer patients nearing the end of life about how they were living with their diagnosis. She was surprised to find that many asked ...

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.