Scientists from Sydney’s Garvan Institute of Medical Research have found gene expression in a prostate cancer cell to be more complex than previously imagined.
Published in Nature Cell Biology, 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.
These biochemical processes (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 is responsible for the physical coiling or structuring of DNA. It can determine whether or not a gene is accessible for interaction with other molecules inside a cell.
“Epigenetic changes reduce the available genome to a point where only the genes that promote cell proliferation are accessible in the cancer cell,” said project leader Professor Susan Clark.
“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 tumour cell is very different from the healthy cell. It also tells us that it works in a programmed rather than a random way, and that it targets a significant part of the genome, rather than just single genes.”
“It tells us that treating cancer will be far more complex than we imagined, as it will first involve understanding and reversing epigenetic change.”
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