Cell death key discovered by Monash Institute

Melbourne researchers have uncovered a new genetic player in programmed cell death, offering a fresh target for potential cancer therapies.

The team from the Monash Institute of Reproduction and Development's Centre for Functional Genomics identified the master gene ETS1 as being critical in the process known as apoptosis.

Centre director Assoc Prof Paul Hertzog said that while it was known ETS1 was a protein transcription factor, or master gene, that regulated other genes, its key role in cell death has not been known until now.

"What our research has shown is that ETS1 is essential for the normal regulation of cell death, and therefore the regulation of cell death in cancer," Hertzog said.

This could lead to future cancer treatments that focused on ETS1 as well as the pathways through which it worked, by enhancing the affect of ETS1 to increase the death of pre-cancerous and damaged cells.

Hertzog said ETS1 was not the only gene implicated in apoptosis, but the new find provided a broader approach.

"It's important to know what all the players are, because the problem with targeting any individual players is that it will probably have limited success and most therapies will have to be multifaceted," he said.

The discovery was made when researchers removed ETS1 from mouse embryonic stem cells as part of the process of developing a knockout animal model. But because of the critical role of ETS1 in programmed cell death, the scientists were unable to generate a mouse and thereby uncovered the gene's important function.

The discovery, jointly made by Hertzog and doctors Dakang Xu and Trevor Wilson, was published in the August 1 issue of the European Molecular Biology Organisation Journal.

Hertzog said the next step, now that ETS1 was identified as a validated target, would be to determine its structure before working on the creation of a drug that could modify the gene's behaviour.

He said the group was currently looking at potential commercialisation and partnering opportunities to develop the cancer therapy avenue.

But he said the function of the gene could also have applications in inflammatory disease and, as such, that research path would be further developed with the new CRC for Chronic Inflammatory Diseases.

The CRC, which involves the University of Melbourne, Monash and the University of Queensland, also has industry support through a partnership with drug giant AstraZeneca.