A breast-cancer expert visits Dublin and talks about new efforts to defeat the disease, writes Kirstin Goldring
Controlling genes in the body is a lot like playing the piano, according to a leading cancer researcher. Just as piano notes join to create a tune, the switches that activate genes work in harmony to oversee normal cell activity.
But just as a pianist can hit sour notes, so too can the controlling switches or "coactivators" hit the wrong chord to trigger disease, states the head of cancer research at Baylor College of Medicine, Houston, Texas, Prof Bert O'Malley.
O'Malley is a world leader in breast cancer research and was in Dublin this week to attended a major three-day international conference organised by the Royal College of Surgeons in Ireland (RCSI). He delivered a keynote presentation on Monday, entitled Nuclear Receptor Coactivators: The missing Links in steroid Action pathways.
The plenary lecture was part of the Fifth International Meeting on Rapid Responses to Steroid Hormones, held at RCSI. The meeting focused on the most important recent developments in the study of "steroid hormones", essential signalling chemicals produced by the glands to control cellular activity.
Steroid hormones are vital for proper functioning of the human body. They control a wide range of functions including sexual development, pregnancy, fat and sugar metabolism and inflammation. The hormones act by entering the cell, binding to a receptor and switching on and off genes involved in these functions.
O'Malley's work has focused on understanding how hormones, specifically female hormones, turn genes on and off in the cell. "When a hormone enters the cells it binds to small protein or receptor. The job of this receptor is to find genes to be turned on," says O'Malley.
In order for this to happen the hormone recruits a second molecule, a "coactivator", a discovery made by O'Malley in the 1990s. "In trying to understand how hormones worked, I made an intuitive guess that there must be some sort of master molecule or gene in the cell, serving to co-ordinate the function of other genes," he explains.
O'Malley guessed as far back as the 1970s that coactivators or master genes were involved. He tried to find them, but the technology of the era was not up to it. "I started looking for them again in the early 1990s and found them in 1995. I didn't realise how important the discovery was at the time."
Their significance is now clear. "They sit above the genes and play them like a piano, they can "touch" and activate the keys but the important thing is that they can play them in harmony," he says.
O'Malley believes that these coactivators are the control that allowed humans to make a jump in evolution. "Mice and yeast do not have this level of organisation, they can hit the keys but they can not play a tune."
Since their discovery researchers have studied how the relevance of coactivators to pathology and medicine. "The coactivator organises multiple independent events in the cell to produce a major functional effect," said O'Malley. He gave examples of "events" such as growth of a cell and changes in metabolism (sugar and fat), in cancer development, inflammation, obesity and diabetes.
Understanding coactivators has told us why some people are more sensitive to diseases, he explained. "We inherit different amounts of coactivators, which causes greater or lesser responses from genes," he says. "For example, if someone inherits more or less of the coactivators for growth, it could mean they have a predisposition or are less likely to develop cancer."
O'Malley says 300 coactivators have been identified in the past five years and of these, 165 have already been associated with human disease.
"The discovery of coactivators has helped understand exactly how some drugs work, where we didn't understand before, for example tamoxifen in breast cancer," says O'Malley.
The College's annual fundraising event, RCSI's Race Against Breast Cancer Day, sponsored by Vivas Healthcare, takes place on November 4th at Leopardstown Racecourse. Last year's event raised €625,000 for research. For further information on how to participate contact RCSI Development Office at 01-4022747 or development@rcsi.ie
Kirstin Goldring is based at Imperial College London and is on placement atThe Irish Times as a British Association for the Advancement of Science Media Fellow