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Humble yeast sheds light on promising anti-cancer drug

SYDNEY, AUSTRALIA The humble yeast has revealed the molecular workings of an anti-cancer drug that stops the growth and spread of tumours in humans by starving their blood supply.

Until now, University of New South Wales scientists who developed the drug (GSAO) knew that it was lethal against endothelial cells but not why it had no direct impact on tumours themselves.

The new study reveals that endothelial cells lack the "transport protein" that tumours use to eject foreign molecules that invade their cell structure.

Endothelial cells are the building blocks of blood vessels. Cancer cells rely on blood vessel growth, known as angiogenesis, to grow and spread to other parts of the body.

"It's very sexy science," says one the research authors, Professor Philip Hogg, a biochemist with the UNSW Centre for Vascular Research and the Children's Cancer Institute Australia. "We now understand how an anti-cancer drug works in humans thanks to genetic studies using the humble yeast cell."

Published in today's edition of the prestigious Journal of the National Cancer Institute, the study reveals how researchers "genetically fingerprinted" the transport protein by using genetically modified (mutant) yeast cells. The researchers used 4800 yeast mutants that represent every non-essential gene in the genome.

"The mutant yeast cells that were vulnerable to the drug lacked the protein that enables them to eject the drug across their cell membrane," says Professor Ian Dawes, a study co-author from the UNSW Ramaciotti Centre for Gene Function Analysis.

"Yeast cells that lacked the protein died, while those that had the protein didn't," says Dawes. "That told us there was a specific gene encoding a protein that's vital for a cell to protect itself against GSAO."

Once the researchers knew this they looked for and found a corresponding protein in humans, known as a multi-drug resistance associated protein (MRP).

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Contact: Professor Philip Hogg
p.hogg@UNSW.EDU.AU
61-423-093-870
University of New South Wales
18-Oct-2005


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