Natural Tumour Suppressor Protein may Herald New Therapies

by Rajashri on Sep 11 2008 2:59 PM

A naturally occurring protein that plays a crucial role in suppressing tumour growth has been identified by researchers from the University of Pennsylvania School of Medicine.

They found that Fbx4, a naturally occurring protein, plays a key role in stopping production of another protein called Cyclin D1, which is believed to contribute to the early stages of cancer development.

The study found that when mutations block production of Fbx4, Cyclin D1 is not broken down, and consequently contributes to cancer's advance.

The researchers suggested that Fbx4 acts like a bouncer, stopping trouble before it starts by breaking down Cyclin D1 before it can affect the body.

"Cyclin D1 was identified nearly 20 years ago and after that, it became apparent that it was overexpressed in a high percentage of tumours," said J. Alan Diehl, PhD, Associate Professor of Cancer Biology at the University of Pennsylvania's Abramson Family Cancer Research Institute.

"But its expression didn't correlate to mutations within Cyclin D1, so we were looking for a protein that regulates accumulation. That's Fbx4," he added.

During the study, the researchers analysed 116 esophageal tumours and found 16 mutations.

The actual mutations researchers found are located within a highly conserved region of Fbx4 that functions like an on switch.

The mutations within that switch region inhibit activation of Fbx4, which means it can't trigger destruction of Cyclin D1.

The results are important in that they show how Cyclin D1 becomes so prevalent in tumours. Before, it was thought that Cyclin D1 was present because of a mutation somewhere in the DNA of a cell.

"Instead, this study shows that Cyclin D1 naturally occurs, but our bodies have created a natural defence mechanism that breaks it down before cancer develops," he added.

Their findings were published in a recent issue of Cancer Cell.