Clues to tumour fighter

Researchers think they have discovered how to boost one of the body's natural cancer fighters.

It might be possible to superpower the gene, known as PTEN, by tinkering with an enzyme that regulates its activity, scientists report in the January 12 issue of Cell.

Although they are a long way from developing an actual drug based on the discovery, the ability to manipulate the tumour-suppressor gene is "potentially a real breakthrough," said study author Dr Pier Paolo Pandolfi, a professor of cancer biology and genetics at Memorial Sloan-Kettering Cancer Centre.

Pandolfi and other researchers at Sloan-Kettering and Columbia University were intrigued by the PTEN gene, which suppresses tumours by preventing "excessive proliferation [of cells] that's associated with cancers and [inducing] cells to die when they misbehave and act as a tumour," Pandolfi explained.

Gene acts like a guard
Essentially, the PTEN gene acts as a guard inside a cell, explained Xuejun Jiang, director of a Sloan-Kettering laboratory that studies cells. But when the gene mutates, it stops guarding cells properly.

"The consequence is that those cells might grow crazily, and when they need to die, they don't die," Jiang said.

Scientists have noticed that mutated PTEN genes seem to be connected to several kinds of cancer, including tumours in the prostate, brain and breast.

Enzyme in control of gene
In three new studies, published in the January 12 issue of Cell, researchers report that an enzyme known as NEDD4-1 appears to be crucial in telling the PTEN gene what to do. Essentially, the enzyme regulates PTEN, which is itself a regulator, Jiang explained.

If there's more of the enzyme, the PTEN gene seems to do a shoddier job of keeping an eye on keeping cancer at bay. That made the scientists wonder whether they could control tumours by manipulating the levels of the enzyme.

"Now we are trying to build up more sophisticated cell models and animal models" to confirm whether this approach would work, Jiang said.

Tinkering could be risky
There's at least one possible hitch: tinkering with PTEN could be devastating, according to Pandolfi, because boosting its power could make the gene go after healthy cells.

That would, in essence, make a treatment toxic, just like current chemotherapy drugs sometimes poison the body as they kill the cancer.

This isn't the first time researchers have looked at PTEN. In 2005, researchers at Sloan-Kettering reported that the gene could stop massive tumour growth in prostate cancer even when another tumour suppressor, known as P53, was turned off.

In those cases, PTEN seemed to make mutating cancer cells go to sleep. – (HealthDayNews)

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Cancer Centre

January 2007