New genes which help prevent prostate, skin and breast cancer development in mice have been discovered by researchers at the Wellcome Trust Sanger Institute and their collaborators.
The study identified genes that cooperate with the well-known tumor suppressor gene PTEN, and showed their relevance in human prostate tumors.
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 tumors, and endometrial cancers.
Tumor 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 tumor suppressor gene that co-operated with Pten.
The researchers analysed 278 prostate, breast and skin tumors from the mice and revealed hundreds of genes that could cooperate with PTEN and act as further tumor suppressor genes.
Human cell lines and data from human prostate tumors were then used to study the five most promising genes.
Dr Juan Cadiñanos, joint lead author, said: “This is the first study to look specifically for tumor suppressor genes that cooperate with PTEN in a range of cancer types.”
“We found that genetically inactivating PTEN and each of the five candidate genes in human cell lines did drive cancerous changes in the cells.”
“We also discovered that human prostate cancer samples had lower levels of expression from the five genes than usual, indicating that these pathways may be important for suppressing tumors.”