'Defence' gene reveals how oestrogen fuels cancer

Cancer Research UK

CANCER RESEARCH UK scientists have shown for the first time how a natural 'defence' gene involved in fighting infections such as common colds, can be triggered by hormones to ignite and drive cancers like breast, ovarian, and possibly prostate cancer. Their findings are published in the Journal of Experimental Medicine*.

A team of researchers at Clare Hall Laboratories, in Cancer Research UK's London Research Institute, have shown that the female hormone oestrogen is able activate the AID** protein. There is strong evidence that abnormally high levels of the AID protein can mutate genes responsible for cell growth - which could lead to cancer. This discovery could explain how hormones fuel some cancers and provide a lead to future research on prevention and treatments.

The AID protein is typically involved in normal healthy immune responses. It enables the body to make thousands of different antibodies needed to fight infections.

Lead author Dr Svend Petersen-Mahrt, head of the London Research Institute's DNA Editing laboratory said: "We know that mutations in some of our genes can cause cells to grow in an uncontrolled manner - leading to cancer. But it was not fully understood how hormones like oestrogen fuel those mutations in some forms of the disease - although we knew there was a strong connection. This research shows that AID is could be the missing link."

The international team of scientists***, discovered this link by treating cells with the hormone oestrogen in the laboratory and analysed the effect of the hormones on the level of DNA mutations.

Dr Petersen-Mahrt continued: "Knowing how AID connects oestrogen to cancer is an important discovery. There are around 45,000 new cases of breast cancer in the UK each year and three quarters of these are thought to be fuelled by the hormone. But all women produce oestrogen and most of them will not develop a hormone induced cancer, so we now need to find out what other genetic and environmental factors trigger the disease in some cases and not others."

Dr Lesley Walker, director of cancer information at Cancer Research UK said: "This finding is very important because scientists have long wrestled with the task of explaining the link between oestrogen and cancer even though we knew it was core to the fight against the disease. The link is particularly pertinent to women receiving increased amounts of oestrogen for prolonged periods of time - during Hormone Replacement Therapy (HRT) for instance - because it can increase their risk of developing cancer.

"Knowing how the mutations are fuelled could help us find new ways to stop the oestrogen from activating the AID gene - potentially treating and possibly even preventing cancer. But AID is also very an important defence against infections and does not by itself do any harm. So we would need to be very careful about interfering with the way the gene works."

ENDS

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Notes to Editor

*Siim Pauklin and Svend Petersen-Mahrt, Estrogen directly activates AID transcription and function, Journal of Experimental Medicine, 12 January 2009.

** AID stands for Activation Induced Deaminase. This work looked at both the gene AID and the protein AID. It found that oestrogen binds to the AID gene which then produced higher levels of AID protein and ultimately mutations in some of the growth controlling genes.

***This work was a collaboration between the DNA Editing Lab, Cancer Research UK Clare Hall Laboratories and the DNA Hypermutation and Cancer Group, Spanish National Cancer Research Center.

About hormones and cancer

Hormones are natural chemicals that are made by glands in our bodies. They are carried in our bloodstream and act as messengers between one part of our body and another. They control the growth and activity of certain cells and organs.

Some cancers such as breast, womb and prostate cancers are stimulated by hormones so treatments have been developed to block them. To find out more about hormone treatments for cancer go to CancerHelp UK.

About the London Research Institute

The Cancer Research UK London Research Institute (LRI) conducts innovative basic biological research to improve our understanding of cancer. The LRI has 550 staff and students and houses 46 research groups based at two locations: Lincoln's Inn Fields laboratories in central London, and Clare Hall laboratories on London's outskirts at South Mimms, Hertfordshire. For more information visit www.london-research-institute.co.uk

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