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What it might take to unravel the 'lean mean machine' that is cancer
Date:2/23/2010

Scientists from Sydney's Garvan Institute of Medical Research have published a paper, online today in Nature Cell Biology, describing gene expression in a prostate cancer cell: more sweeping, more targeted and more complex than we could ever have imagined, even five years ago.

The study shows that changes within the prostate cancer cell 'epigenome' (biochemical processes that target DNA and affect gene expression) alter the expression of many genes, silencing their expression within large regions of DNA nearly 3% of the cell's genome.

Epigenetic 'events' include 'DNA methylation' and 'chromatin modification'. Methylation occurs when a methyl group - one carbon atom and three hydrogen atoms - attaches to a gene, determining the extent to which it is 'switched on' or 'switched off'. Chromatin, responsible for the physical coiling or structuring of DNA, can determine whether or not a gene is accessible for interaction with other molecules inside a cell.

Project leader Professor Susan Clark describes the typical cancer cell as a 'lean mean machine'. "Epigenetic changes reduce the available genome to a point where only the genes that promote cell proliferation are accessible in the cancer cell," she said.

"We can see that the epigenome is remodelled in a very consistent and precise way, effectively swamping the expression of any gene that goes against the cancer cell's interests."

"The swamping encompasses tumour suppressor genes, and all the neighbouring genes around them, as well as non-coding RNA, intergenic regions and microRNAs. Only those genes essential for growth activation are allowed to be active, while all the genes and regions that apply brakes are inactivated."

"We now have an epigenomic map of the prostate cancer cell which we didn't have before. That has taken three years to develop, including the technology and methods to interpret our tissue samples."

"The map tells us that the
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Contact: Alison Heather
a.heather@garvan.org.au
61-292-958-128
Research Australia
Source:Eurekalert

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