Navigation Links
Stabilizing cancer-fighting p53 can also shield a metastasis-promoter

HOUSTON - Efforts to protect the tumor-suppressor p53 could just as easily shelter a mutant version of the protein, causing cancer cells to thrive and spread rather than die, according to research by scientists at The University of Texas M. D. Anderson Cancer Center reported in the current issue of the journal Genes and Development.

"As we develop therapies to restore the function of p53, we need to make sure we first know what version of this gene is present in a patient's tumor and then decide how to treat it," said senior author Guillermina Lozano, Ph.D., professor and chair of M. D. Anderson's Department of Cancer Genetics.

The research shows that attempting to restore normal expression of p53 protein by blocking another protein that normally degrades p53 can have the perverse effect of protecting mutated p53 and promoting metastasis.

The p53 gene is inactivated in many types of cancer. Its normal role is to halt the division of a defective cell and then force the cell to kill itself or deprive the cell of its ability to reproduce. As such, reactivation of p53 is thought to have great therapeutic potential.

Normally, p53 levels are low, but it springs into action in response to DNA damage or activation of cancer-promoting genes, or oncogenes.

Lozano, an expert on mouse models of human cancer, and colleagues developed mice with a specific mutation of p53 that mimics a common genetic mutation in human cancers. The mutated gene, called p53H, expresses a defective version of the p53 protein.

When mice had the p53H mutation on both genes (p53 H/H), the researchers found that the p53 protein was not detectable in normal tissue but was present in 79 percent of tumors. However, tumors in these mice did not metastasize.

Enter Mdm2, a protein whose normal job is to degrade p53 when it's no longer needed. Mdm2 also degrades the mutated version of the p53 protein.

The researchers developed p53 mutant mice that lacked one or both copies of Mdm2. Mice with the double-mutant p53 that also had no Mdm2 died sooner and developed more aggressive metastatic tumors than mice with only the p53 mutation.

The frequency of metastasis went from zero in the p53 H/H with normal Mdm2, to 9 percent in mice lacking one copy of Mdm2 to 17 percent in mice with no Mdm2. Metastasis - the invasive spread of cancer to other organs - causes 90 percent of all human cancer deaths.

Absence of a second tumor-suppressing gene, p16, also promotes stability of mutant p53.

"The importance of this study cannot be overemphasized," the researchers concluded. Drugs that try to protect normal p53 by inhibiting the p53-degrading protein Mdm2 also would protect mutant p53 "with dire consequences."

By the same token, chemotherapy that seeks to stabilize p53 could also stabilize the mutant version. Detecting the type of p53 present in a tumor is possible with current lab technology, Lozano said.

The study raises the possibility of suppressing cancer metastasis by eliminating mutant p53 stability, which the researchers note is more feasible than converting mutant p53 to the normal type.


Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center

Related medicine news :

1. Skin flaps deliver cancer-fighting therapy, ASPS study reveals
2. Alvarado Hospital Files Countersuit Against Blue Shield
3. BlueCare(R) Family Plan, a HUSKY Health Plan from Anthem Blue Cross and Blue Shield in Connecticut, Raises Awareness, Funds and Diapers for New Haven Diaper Bank
4. Blue Cross Blue Shield of Michigan Corrects News Story about Drug Coverage Announcement
5. Karen Vigil Named Senior Vice President and Chief Executive Officer, Blue Shield of Californias Individual, Small Group, and Government Business Unit
6. Highmark Blue Cross Blue Shield Introduces New Health Plan Comparison Tool for Consumers
7. Highmark Blue Shield Introduces New Health Plan Comparison Tool for Consumers
8. Blue Cross and Blue Shield Initiatives Recognized for Increasing Patient Safety and Efficiency
9. Blue Cross and Blue Shield of Florida Reports Eighteenth Consecutive Year of Positive Performance
10. Blue Cross Blue Shield of Michigan Offers New Approach to Customer Group Wellness
11. Blue Cross and Blue Shield Association Holds Forum to Explore Patient Safety and Healthcare Quality Initiatives
Post Your Comments:
Related Image:
Stabilizing cancer-fighting p53 can also shield a metastasis-promoter
(Date:6/27/2016)... Aliso Viejo, California (PRWEB) , ... June 27, 2016 , ... ... that are fully customizable inside of Final Cut Pro X," said Christina Austin - ... with another unique style. Final Cut Pro X users can now reveal ...
(Date:6/27/2016)... ... June 27, 2016 , ... ... payment industry today announced its strategic partnership with Connance, a healthcare industry ... The two companies’ proven, proprietary technology combine to provide health systems, hospitals ...
(Date:6/27/2016)... , ... June 27, 2016 , ... recently awarded ... Eyeglasses . , Millions of individuals in the United States and Canada wear ... a way to both correct vision and make a fashion statement. Even celebrities use ...
(Date:6/26/2016)... ... , ... On June 10-11, 2016, A Forever Recovery, a holistic treatment center ... Breakfast Table in Battle Creek, MI, where the rehabilitation facility is located. This annual ... the world’s leading providers of cereal and other breakfast foods. Its residents often refer ...
(Date:6/26/2016)... Carolina (PRWEB) , ... June 26, 2016 , ... ... of a new product that was developed to enhance the health of felines. The ... centuries. , The two main herbs in the PawPaws Cat Kidney Support ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016   Bay Area ... Network,s Dean Center for Tick Borne Illness ... and Rehabilitation, MIT Hacking Medicine, University of California, ... today announced the five finalists of Lyme ... disease.  More than 100 scientists, clinicians, researchers, entrepreneurs, ...
(Date:6/24/2016)... 24, 2016 Dehaier Medical Systems Ltd. (NASDAQ: ... develops, markets and sells medical devices and wearable sleep ... a strategic cooperation agreement with Hongyuan Supply Chain Management ... on June 20, 2016, to develop Dehaier,s new Internet ... agreement, Dehaier will leverage Hongyuan Supply Chain,s sales platform ...
(Date:6/24/2016)... 24, 2016   Pulmatrix, Inc ., (NASDAQ: ... inhaled drugs, announced today that it was added to ... its comprehensive set of U.S. and global equity ... an important milestone for Pulmatrix," said Chief Executive Officer ... of our progress in developing drugs for crucial unmet ...
Breaking Medicine Technology: