Finding the genes that help testosterone drive prostate cancer

Why did we fund this project?

• Prostate cancer relies on a hormone called testosterone to be able to grow and spread rapidly.
• Hormone therapy stops testosterone from being produced, and this slows the growth of prostate cancer.
• Testosterone helps prostate cancer grow by turning on certain genes in prostate cancer cells. These genes produce proteins that help prostate cancer grow and spread.
• In this project, Professor David Elliot and team wanted to know which of these genes are most important in driving prostate cancer growth, to identify targets for new prostate cancer treatments.

What did the team do?

• The team studied prostate cancer cells before and after they were exposed to testosterone, and identified genes that were turned on or off.
• They then studied these genes in prostate cancer tissue from men, to narrow down to a few candidate genes that link testosterone and prostate cancer.
• These candidate genes were then investigated in special prostate cancer cells grown in the lab, where the researchers were able to deliberately turn each gene on and off. By doing this, they could work out how each gene impacted prostate cancer growth.

What did the team achieve?

• The team found over 6000 genes that are changed by testosterone in prostate cancer cells, and used data from men’s prostate cancer tissue to filter down to a smaller number of candidate genes to study further.
• Among these was a gene called TSC1. The team were particularly interested in this gene as it is usually important for stopping the growth of cancer. However, testosterone seems to make this gene switch sides, and help cancer to grow.
• Testosterone also increased production of an enzyme that makes a specific class of sugars called glycans. Glycans help prostate cancer to grow and spread to other places in the body, and the team think they could be an important link in how testosterone helps prostate cancer to grow and spread. They are investigating it further in a new project.

How does this benefit men?

• The team have uncovered lots of genes that are important in helping testosterone drive the growth of prostate cancer. The team now want to investigate these genes further, to identify which are the best targets for new treatments.
• The finding that a sugar enzyme is important in driving prostate cancer growth has led to a new Prostate Cancer UK-funded project led by one of the team members (Dr Jennifer Munkley). This project aims to develop new treatments and diagnostic tests.