Fed: Scientist stumbles on cancer clue

AAP General News (Australia)
04-03-2005
Fed: Scientist stumbles on cancer clue

By Janelle Miles, National Medical Correspondent

BRISBANE, April 3 AAP - It was a stroke of luck all scientists dream about, an accidental
discovery that may one day lead to better treatments for bone and brain cancers.

Sydney researcher Wei-Qin Jiang wanted to observe the inner workings of a cancer cell.

So he added excess amounts of a protein, known as Sp100, into the large doughnut-shaped
structures found in some cancer cells' nuclei.

He coloured the protein molecules fluorescent green to watch their movements under
a microscope and found, to his surprise, Sp100 switched off one of only two known mechanisms
that allow cancer cells to multiply unchecked.

The mechanism, known as ALT - or alternative lengthening of telomeres - is active in
about 10 per cent of all cancers.

Telomeres have been described as protective caps on the end of chromosomes, like plastic
tips on the end of shoelaces.

Once the telomeres of a normal cell become too short, it can no longer continue multiplying.

In certain cancers - like adult brain tumours known as glioblastomas and bone cancers
called osteosarcomas, which particularly affect teenagers and young adults - lengthening
of the telomeres through the ALT process allows the cells to proliferate.

"Discovering how to turn off ALT is a major clue toward developing a treatment for
these cancers," said Roger Reddel, head of cancer research at the Children's Medical Research
Institute, where Dr Jiang works.

"We've known about this process for about 10 years and now for the first time we know
some of the molecules which are involved."

Dr Jiang found large amounts of the Sp100 locked up a complex of three other proteins
which was enough to stop the ALT process - like switching off a light.

"They were rendered inactive by having too much Sp100," Dr Reddel explained.

Finding a drug to mimic Sp100 and turn off the ALT mechanism could save lives with
high-grade glioblastomas almost universally fatal.

But Dr Reddel warned drug treatment could be many years away.

"It's a long way from finding a drug unless we're extremely lucky and find some existing
medicine that interferes with those three proteins," he said.

"That would be another really lucky break.

"Otherwise, what we would try to do is find a small molecule which is able to interact
with those three proteins in the same way that Sp100 does to interfere with their action.

"But it wouldn't be Sp100 itself. It's too big for us to easily deliver it as a drug."

The research was published in the April edition of Molecular and Cellular Biology.

AAP jhm/rll/sd

KEYWORD: CANCER

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