Reported in Nature Genetics, this research sheds light on new pathways involved in cancer development — these could be possible drug targets for cancers with a faulty PTEN gene. The methods developed could also identify other genes that cooperate to suppress cancer growth.
Prostate cancer is the second most common cancer in men in the UK with around 47,000 men diagnosed each year. More than half of prostate cancers have an altered or missing PTEN gene, as do many other cancers, including brain tumours, and endometrial cancers.
Tumour suppressor genes such as PTEN help prevent cancer development in healthy people. PTEN regulates an important cell pathway for growth and division. However, little is known about which other genes and pathways cooperate with PTEN to prevent cancer.
In this study, researchers designed a new method in mice in which part of the Pten gene was converted into a mobile DNA element known as a transposon. When this was mobilized from the Pten gene it was inactivated. Importantly the transposon carrying a piece of Pten would land randomly throughout the genome, damaging genes into which it inserted. Cancers would grow when the transposon damaged a tumour suppressor gene that co-operated with Pten.
Dr Jorge de la Rosa, the first author on the study from the Wellcome Trust Sanger Institute, said: “We developed a new method that coupled Pten inactivation with mobilization of the transposon. We inserted the transposon directly inside the Pten gene, so that whenever it jumped out and inserted into another part of the genome, it inactivated Pten at the same time. By analysing which genes were disrupted in the cancers that grew, we were able to pinpoint genes that cooperate with Pten in suppressing tumours.”