Singapore team shed light on tumour suppressor gene

In collaboration with the Press Association

Scientists working in the lab of Cancer Research UK's chief scientist Professor Sir David Lane have shed more light on the role of a gene called p53, which is known to be faulty in the majority of cancers.

p53 is a tumour suppressor gene that is often referred to as the 'guardian of the genome' because of its role in detecting DNA damage and preventing the growth of cancerous cells.

However, the gene is faulty in over 50 per cent of all cancers, meaning that damaged cells survive and are able to multiply uncontrollably and form tumours.

Researchers at the Agency for Science, Technology and Research's Singapore Immunology Network (SIgN) have discovered how p53 is able to switch other genes 'on' or 'off' by recognising specific DNA sequences, known as response elements.

The discovery takes scientists a step closer to understanding the fundamental biology of cancer, which will in turn inform efforts to develop new anti-cancer therapies.

Scientists at SIgN analysed known p53 response elements and identified a short sequence in all of them that allowed them to predict whether p53 would switch a gene on or off.

Professor Lane, who was involved in the original discovery of p53, described the findings as "intriguing".

"The precise interaction of p53 with its response elements has been studied for some 20 years and, while we have a good understanding of how p53 turns on genes, no clear answer as to the equally important question of how p53 turns off or 'represses' genes has emerged," he explained.

"The SIgN group's identification of a bona fide 'repressive' response element has provided the missing piece which has eluded p53 researchers for a long time, as well as a definitive key with which to perform future studies.

"I expect their findings to have a very positive and significant impact on the progress of biomedical research and to help define this vital tumour-fighting pathway."

Lead researcher Professor Ren Ee Chee revealed that the team had come at the problem from a rather unusual angle as their research actually focuses on immunology.

The researchers wanted to determine the role of p53 because it controls a metastasis gene involved in liver cancer that they had been investigating.

"Our findings illustrate how exciting science can be when innovative discoveries can arise from unexpected sources," Professor Ren said.

"They are also proof that frequently in nature, what may seem very complicated at first eventually turns out to be simple and elegant."

Professor Paola Castagnoli, scientific director of SIgN, said that the study could have "significant and far-reaching implications", allowing the involvement of many genes to be confirmed and possibly uncovering new cellular pathways in which p53 is involved.

"It also clarifies our understanding of which cellular pathways are damaged by p53 mutations and points to areas where new cancer targets might be discovered," she said.

"I am proud of the group's achievements thus far, and look forward to more exciting findings from them."

The team's findings have appeared in the Proceedings of the National Academy of Sciences and Nature Reviews Cancer.

References

Wang, B., Xiao, Z., & Ren, E. (2009). Redefining the p53 response element Proceedings of the National Academy of Sciences, 106 (34), 14373-14378 DOI: 10.1073/pnas.0903284106