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Eliminating tumour suppressor C/EBP alpha explains cancer in ageing liver
Understanding how the tumour suppressor protein C/EBP alpha is eliminated in ageing livers gives important clues to the mechanism by which cancer occurs in that organ and could point the way to new therapies and prevention, said Baylor College of Medicine (www.bcm.edu) researchers in a report that appears online today in the Journal of Clinical Investigation.
A variant of C/EBP alpha called the S193-ph isoform is such a powerful tumour suppressor protein that it must be eliminated before liver cancer can occur, said Dr Nikolai A. Timchenko, professor in the Huffington Centre on Aging and the department of immunology and pathology at BCM.
'Understanding the molecular mechanism behind the development of liver cancer will help develop new ways to prevent the disease,' he said.
The process is multi-step. Another protein - gankyrin, short for gann ankyrin repeat protein (Gann means cancer in Japanese) - must be elevated first.
'It is a small molecule that is part of the protein degradation system in the cell,' he said. 'Previously, it has been shown that this protein eliminates the p53 and RB (retinoblastoma) proteins, both tumour suppressor proteins in other cancers. This is a tumour suppressor killer.'
To demonstrate how the mechanism works, he and his colleagues compared tissues from young mice expressing a specific variant of C/EBP alpha and tissues from wild type old mice. If part of the liver is removed in these mice, this tumour suppressor prevents generation of new liver tissue - indicating that it stalls rapid growth. Uncontrolled growth is a hallmark of cancer.
In these special mice, they found that gankyrin plays an important role in making C/EBP alpha a target for degradation within the cell.
'Cancer is increased in many tissues of older people,' he said. 'The information we have is specific for the liver, but it might also be important for other kinds of cancer. We do not know yet.'
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