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Last Updated: Saturday, 23 July 2005, 23:12 GMT 00:12 UK
Cell death mark liver cancer clue
Image of lab work
The researchers hope their lab work will lead to new drugs
Scientists say they have discovered how a protein causes liver cancer - it tags cancer preventing cell machinery for destruction.

The Japanese and UK team first linked gankyrin to liver or hepatocellular cancer, which affects some 250 million people worldwide, five years ago.

Then they discovered that it appeared to encourage DNA synthesis so cells grew unchecked and became cancerous.

Now they say, in Cancer Cell, gankyrin promotes cancer by another pathway too.

Death tag

It puts a death mark on cell machinery tasked with deciding which cells in the liver should continue to divide and replicate their DNA and which should die.

For example, if a cell is infected with a virus the protein p53 - sometimes called the "guardian of the genome" - will send out a signal so the cell commits suicide.

In hepatocellular cancer, this process is disrupted. Instead, gankyrin binds to an enzyme called mdm2, which gives p53 a molecular label that tags it for death.

This could help improve survival rates in the future
Dr Julie Sharp of Cancer Research UK

The marked p53 is then sent to the cell's waste disposer, called the proteasome, where it is broken down and destroyed.

This means damaged cells can continue dividing unchecked in the liver and grow into tumours.

Researcher Professor John Mayer, from Nottingham University, said: "It's amazing that gankyrin controls the two major cancer-controlling mechanisms.

"The cells go on and on dividing and become cancer cells."

He said that although around half of all tumours in the body involved p53 defects, gankyrin only appears to be linked to liver cancer, which might be down to certain properties of this organ.

Drug hope

"The liver is really interesting because the cells divide very slowly, but the cells can regenerate.

"They are in a division limbo, so to speak.

"We think this is why overexpression of gankyrin leads to liver cancer."

Professor Mayer and co-worker Professor Jun Fujita from Kyoto University are now trying to work out the structure of gankyrin in the hope that it will lead to a way to make anti-cancer drugs that block its action.

Currently there are few drugs for liver cancer and no cure.

Dr Julie Sharp, senior science information officer at Cancer Research UK, said: "Identifying some of the molecular events that may contribute to the development of liver cancer provides an important step towards finding better ways of treating this disease.

"This could help improve survival rates in the future."




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