Study sheds light on cancer-causing gene

In collaboration with the Press Association

US scientists have discovered a previously unknown way by which a cancer-causing version of the Myc gene speeds up the progression of the disease.

A faulty version of Myc is already known to interfere with the early stages of DNA activity in the nucleus of the cell. It prevents DNA from being 'transcribed' into RNA, which is an essential first step in making proteins for cell growth and function.

However, scientists at the University of California San Francisco (UCSF) have now found that the faulty Myc gene can also act directly on the final stage of protein production.

- Ed Yong, health information manager, Cancer Research UK

Dr Maria Barna, a faculty fellow in the university's Biochemistry and Biophysics Department and one of the study's senior authors, explained that cancer-causing genes such as Myc regulate a number of distinct cellular processes.

"The key to our studies was the ability to generate novel genetic tools to halt Myc's action on protein production. This demonstrates how essential this process is for cancer formation," she revealed.

Co-senior author Dr Davide Ruggero, assistant professor of urology at the UCSF Helen Diller Family Comprehensive Cancer Centre, commented: "Control of protein production rapidly affects cell behaviour, and in a robust manner.

"The ability of the Myc oncogene to directly alter this process may well explain the rapid progression of cancer formation."

In order to find out whether Myc-induced protein production plays a role in cancer, the researchers bred two types of mice - one of which was prone to cancer and over-expressed the Myc oncogene, while the other had lowered protein production.

This resulted in mice which had the destructive Myc traits as well as an enhanced ability to suppress protein production.

The researchers found that in these mice, cell growth, division and death - which is required to counter cancer - were restored to near-normal levels.

This also helped to counter Myc-induced damage to chromosome function, indicating that Myc causes changes in the genetic integrity of cells through control of protein production and that it may disrupt a number of genes.

Dr Ruggero said: "We discovered a previously unrecognised link between alterations in protein synthesis and the mechanism by which cells maintain the integrity of the genome.

"We found that when Myc is overexpressed, this leads to changes in protein levels of a key gene that is essential for normal distribution of genetic material between daughter cells during cell division."

The discovery, which appears in Nature, suggests that existing drugs which counter increased protein production could slow down tumour growth in cancers where Myc is overactive.

Ed Yong, Cancer Research UK's health information manager, said: "Genes like Myc contribute to cancer in many different ways and every time we discover a new one, we give ourselves another potential avenue for beating the disease."

Ref: Barna et al. Nature 456, 971-975 (18 December 2008)

References

Maria Barna, Aya Pusic, Ornella Zollo, Maria Costa, Nadya Kondrashov, Eduardo Rego, Pulivarthi H. Rao, Davide Ruggero (2008). Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency Nature, 456 (7224), 971-975 DOI: 10.1038/nature07449