Posts Tagged ‘sleeping beauty transposon’

Curator: Ritu Saxena, Ph.D.

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Introduction and Research Relevance:

Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer death in the United States with a median survival of <6 mo and a dismal 5-yr survival rate of 3%–5%. The cancer’s lethal nature stems from its propensity to rapidly disseminate to the lymphatic system and distant organs. This aggressive biology and resistance to conventional and targeted therapeutic agents leads to a typical clinical presentation of incurable disease at the time of diagnosis.


Also, it has been well documented that despite much progress in its molecular characterization, Pancreatic ductal adenocarcinoma (PDA) remains a lethal malignancy.

Recent article published in the journal Nature talks about discovering the link between a gene and the prognosis of Pancreatic Ductal Adenocarcenoma (PDA). The discovery might have therapeutic relevance in PDA.

Although previous work had attributed a pro-survival role to USP9X in human neoplasia, the researchers found instead that loss of Usp9x protects pancreatic cancer cells from death. Thus, the study proposed USP9X to be a major tumour suppressor gene with prognostic and therapeutic relevance in PDA.


News brief: (http://www.sanger.ac.uk/about/press/2012/120429.html)

29 April 2012

Gene against pancreatic cancer discovered

Study points to potential new treatment for deadly pancreatic cancer

In a study published in Nature (Sunday 29 April), researchers have identified a potential new therapeutic target for pancreatic cancer.

The team found that when a gene involved in protein degradation is switched-off through chemical tags on the DNA’s surface, pancreatic cancer cells are protected from the bodies’ natural cell death processes, become more aggressive, and can rapidly spread.

Pancreatic cancer kills around 8,000 people every year in the UK and, although survival rates are gradually improving, fewer than 1 in 5 patients survive for a year or more following their diagnosis.

Co-lead author Professor David Tuveson, from Cancer Research UK’s Cambridge Research Institute, said: “The genetics of pancreatic cancer has already been studied in some detail, so we were surprised to find that this gene hadn’t been picked up before. We suspected that the fault wasn’t in the genetic code at all, but in the chemical tags on the surface of the DNA that switch genes on and off, and by running more lab tests we were able to confirm this.”

The team expects this gene, USP9X, could be faulty in up to 15 per cent of pancreatic cancers, raising the prospect that existing drugs, which strip away these chemical tags, could be an effective way of treating some pancreatic cancers.

” This study strengthens our emerging understanding that we must also look into the biology of cells to identify all the genes that play a role in cancer. ” Dr David Adams

“Drugs which strip away these tags are already showing promise in lung cancer and this study suggests they could also be effective in treating up to 15 per cent of pancreatic cancers,” continues Professor Tuveson.

The researchers used a mouse model of pancreatic cancer to screen for genes that speed up pancreatic cancer growth using a technique called ‘Sleeping Beauty transposon mutagenesis’. This system uses mobile genetic elements that hop around the cell’s DNA from one location to the next. Cells that acquire mutations in genes that contribute to cancer development will grow out and ‘driver’ cancer genes may be identified.

By introducing the Sleeping Beauty transposon into mice pre-disposed to develop pancreatic cancer, the researchers were able to screen for a class of genes called a tumour suppressor that, under normal circumstances, would protect against cancer. These genes are a bit like the cell’s ‘brakes’, so when they become faulty there is little to stop the cell from multiplying out of control.

This approach uncovered many genes already linked to pancreatic cancer. But unexpectedly, USP9X, was identified.

Co-lead author Dr David Adams, from the Wellcome Trust Sanger Institute, said: “The human genome sequence has delivered many promising new leads and transformed our understanding of cancer. Without it, we would have only a small, shattered glimpse into the causes of this disease. This study strengthens our emerging understanding that we must also look into the biology of cells to identify all the genes that play a role in cancer.”


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