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Mutant p53 DNA breaks and contributes to the development of cancer

November 7, 2018 14:52

Researchers in Melbourne found that the development of tumors caused by mutations in the p53 gene.

Research has shown that in the early stages of cancer the mutant gene can no longer activate the natural protection, such as the DNA repair process of the organism. The findings appear in the issue of Genes and Development.

p53 is known as the "guardian of the genome" because of its role in protecting against cancer cells.

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«P53 plays an important role in many of the ways that prevent cancer, for example, in DNA repair or killing cells if they have the irreparable DNA damage, - said Dr. Gemma Kelly, a researcher. - Genetic defects in p53 are found in half of all human cancers, but exactly how these changes violate the p53 function is a mystery. "

Cells usually have two copies of the p53 gene. At the beginning of tumor development, one copy is subject to constant change due to mutations, while the other copy is normal. As a result, the cell forms a mixture of normal and mutant copies of p53.

Scientists have discovered that a mutant p53 protein may bind with normal p53 and block execution of its protective role, such as DNA repair. This makes the cell more susceptible to further genetic changes that accelerate the development of tumors.

A team of researchers had expected that the mutant proteins to block all normal activity of p53, so was surprised that they were affected only certain p53-dependent pathways.

"The mutant proteins behave slyly while they stop p53 from activating pathways that protect against cancer, yet they allow p53 to activate pathways that promote tumor growth. The role of p53 in cancer is clearly more difficult than we expected, "- Dr. Kelly says.

 "For decades, scientists discuss how the mutant p53 affects the development of cancer. Some argue that the mutant p53 is struggling with the normal protein and blocks its natural protective role. Others believe that the mutant p53 is the "outcast" and perform new roles that contribute to tumor development. Our work clearly demonstrates that while cancer is the most important fight of normal p53, that selectively disables some, but not all of the normal functions of p53, "- says Professor Andreas Strasser.

Currently, researchers are studying how this is true for tumors formed, which is very important for the therapy.

"Formed tumors often lose their normal copy of the gene p53 and produce only mutant p53, - Dr. Kelly says. - If the mutant p53 acts by treatment of normal p53, it can no longer play a role in the tumor, where no normal p53. This would mean that drugs that block the mutant p53, would not be of clinical benefit. Conversely, if the mutated p53 has a new, contributing to the development functions in their own cancer tumors, the drug that specifically blocks the mutated p53 may be useful for the treatment of thousands of patients. "

Source: https://medicalxpress.com/news/2018-11-mutant-protein-tackles-dna-guardian.html

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