Melbourne scientists have discovered how tumor development is driven by mutations in the most important cancer prevention p53 gene.
The research revealed, in the early stages of cancer, that p53s were going to address & # 39; A normal p53 protein that blocks to discharge its defensive role. As a result, p53 can no longer act natural defenses against cancer – such as the body's DNA repair process – increasing the risk of developing cancer.
The research led by Dr Brandon Aubrey, Professor Andreas Strasser and Dr Gemma Kelly together with Professor Gordon Smyth and Dr. Yunshun Chen bio-awareness. The findings are published in this month's edition Genes and Development.
Researchers have discovered how mutations in p53 – found in half of all human cancers – drive cancer development.
The mutant p53 protein is going to & # 39; with normal protein and prevent it from discharging its protective role, while enabling it to stimulate genes that cause tumor growth.
The team is now exploring whether the mutant p53 protein operates in the same way as established tumors, with important implications for cancer therapy.
Going to a DNA guardian
P53 is called the genome guardian; because of its role in protecting cells from cancer.
"P53 plays an essential role in a number of paths that prevent cancer, such as repairing DNA or killing cells if they have an unpleasant DNA damage," said Dr Kelly.
"Genetic shortcomings in p53 find half of all human cancers, but exactly the way these changes disrupt the role of p53 has been a mystery for a long time."
Dr Kelly said that cells usually had two copies of the p53 gene in each cell.
"Early in cancer development, one copy of the gene can have a sudden and lasting change by rolling, while the other copy of the gene remains normal. This means that the cell make a mixture of normal and mutant versions of the p53 protein.
"We found that the mutant p53 protein can bind the normal p53 protein, preventing it from carrying out defensive roles such as DNA repair, which makes the cell more likely to have further genetic changes that accelerate development tumors. "
The team expected that mutant proteins would block all normal p53 activity, so we were surprised to find that only some p53-dependent paths were affected.
"The mutant proteins are confidential: while preventing p53 from mitigating cancer-protected pathways, they still allow p53 to operate pathways that promote tumor growth. The role of p53 in cancer is obviously more complicated than we had expected, "said Dr Kelly.
Mystery was solved
Professor Strasser stated that the findings reported a long-term debate about the mutant p53.
"Scientists have been discussing how p53 mutants contribute to cancer development for decades.
"One camp argues that a mutant p53 is activated by routine addressing and preventing its natural defense roles. The other camp argues that The p53 mutant flinks and performs new roles that promote tumor development. "
"Our work clearly shows that during the development of cancer, normal shutdowns are most significant. This disables specific p53 extracts, but not all, usually," he said. Professor Strasser.
The team is now investigating whether the same is true for established tumors, with important implications for drug treatments.
"Established tumors have often lost the normal copy of their p53 gene and only produce mutant p53 protein," said Dr Kelly.
"If a mutant p53 is activated by using normal p53, more time may not be involved in established tumors where normal p53 is not produced. This would mean that there would be no blocking drugs p53 mutant gets no clinical benefit, "he said.
"Against the case, if p53 mutant has new activities that promote cancer itself in established tumors, then a drug that blocks p53 mutant may be beneficial to treat thousands of patients."