Researchers at Children’s Medical Research Institute (CMRI) have published in Clinical Epigenetics about a protein found to play an important role in cancer cell division. The research found that by depleting the BRG1 protein in cancer cells, genes involved in DNA replication were repressed. This finding reveals new insight into how cancer cells spread and hints at new drug targets in cancer treatment.
The research was the brainchild of Dr Kate Giles in the Genome Integrity unit at CMRI, who started looking at the BRG1 protein eight years ago. “The initial work, performing RNA sequencing on prostate cancer tissue, was performed as part of my PhD in 2014, so this has been a long journey and it’s great to see it complete and published,” Dr Giles said. “There have been four or five studies on the over-expression of BRG1 in cancers, but our research is different because we’re looking at why this overexpression of BRG1 matters. We wanted to know what it does.”
Dr Giles and her fellow researchers used prostate cancer samples to examine the pathways within a cell that were affected by BRG1. They found that certain genes behaved differently in the presence of BRG1, and all these genes had a role in cell division. Once they knew that which genes were affected by BRG1, the researchers depleted BRG1 and found it inhibited cell division.
This action of the BRG1 protein comes under what biologist call ‘epigenetics’. Epigenetics is the study of how the same base genetic information in DNA can produce different outcomes in different cells. While our DNA remains the same in every cell, genes can be turned on, turned off, or repressed by proteins present in the cell. The protein BRG1, part of the larger SWI/SNF protein (pronounced swee-sniff), makes physical changes to the scaffolding on which genetic information sits (chromatin remodelling), altering which genetic information is ‘accessible’ and which proteins are able to be produced.
“We can think of DNA as a paragraph of text on a page with all the core information about a person,” Dr Giles explained. “Epigenetics is like the punctuation, the highlighting, and the crossing-out which gives different emphasis to the text. Through epigenetic processes, the same core text can be read differently in different cells or under different conditions. We can highlight text that is particularly important to a cell, or we could redact certain words or phrases. These changes can turn genes on or off in specific cells.”
Moving to CMRI was able to help Dr Giles understand why the overexpression of BRG1 was important in cancer cells.
“Confirming the functional effect of BRG1 has been the majority of my research here at CMRI. Coming to CMRI was where the research took off because of the particular expertise of the people here. Being able to collaborate with colleagues who were experts in cell cycle processes was particularly helpful.”
Dr Giles speculated on BRG1 as a target for cancer drug treatments. “BRG1 would be a nice target for certain leukaemias and some breast cancers. Unfortunately, at the moment there are only two drug inhibitors of BRG1, and the part of the protein they target doesn’t completely stop its function.”
Dr Giles was optimistic on the future of epigenetic research and, in particular, of the importance of chromatin remodelling research. “I do really like this type of research. I’m really glad that it’s led to the project I’m working on now at CMRI. Chromatin remodelling can sometimes be overlooked, but we think that’s changing.”
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