A new article in PLOS Biology from the collaborating groups of Clive Wilson and Deborah Goberdhan in DPAG and Freddie Hamdy in the Nuffield Department of Surgical Sciences is shedding new light on the mechanisms that lead to lethal forms of prostate cancer. Men with advanced prostate cancer are routinely treated with drugs that block the production of the steroid testosterone, which inhibits tumour growth. But within a couple of years, hormone-independent tumour cells emerge, which often still require the testosterone receptor to grow and this will lead to the death of the patient. Such pathological hormone-independent receptor signalling was thought to be unique to cancer cells.
DPAG's Aaron Leiblich, Josephine Hellberg and Aashika Sekar have now shown that prostate-like cells in the fruit fly also require a steroid hormone to grow; this hormone-dependent signalling stimulates secretion of proteins into the seminal fluid to promote fertility, just like the human prostate. However, when male flies mate, the steroid receptor switches to a hormone-independent mechanism when males mate. This stimulates more growth in these cells and drives more secretion, rapidly replacing what has been lost during mating. As in prostate cancer, this switch to hormone-independence involves the activation of proteins that stimulate cells to replicate their DNA.
"When Aaron Leiblich, a surgeon in my lab, first showed that steroids are required for growth of the fly prostate, we set out to genetically manipulate the cells to mirror the pathological switch to hormone-independent growth found in cancer patients," Clive Wilson recalls. "It was a big surprise to finally discover that this switch is a normal physiological process linked to mating."
Aashika Sekar, a third year DPhil student who is continuing the study, added: "We’ve already identified other genes that seem to only control the hormone-independent form of steroid receptor signalling in flies. These genes have also been implicated in prostate cancer, so if we can work out how to inhibit their action in flies, perhaps this will give us new ideas for blocking the lethal form of prostate cancer growth."
The full paper, Mating induces switch from hormone-dependent to hormone-independent steroid receptor-mediated growth in Drosophila secondary cells, is available to read here.
Image Legend (above): The prostate-like cells in the fly male accessory gland that switch to steroid-independent growth (marked by red staining) have a higher turnover of secretory compartments (shown in green) than their neighbours