Researchers at the BC Cancer Agency, an agency of the Provincial Health Services Authority, have found a new clue about the mechanisms that cause spontaneous breast cancers. This evidence is published in the September 2005 issue of the prestigious Journal of the National Cancer Institute.

Led by Drs. Connie Eaves and David Huntsman, this study builds on an earlier BC Cancer Agency-Cambridge University discovery of a link between alterations in the Emsy gene and alterations in the BRCA2 gene. Alterations in BRCA2 are strongly associated with inherited breast and ovarian cancers, but have not been found in spontaneous breast cancers.

Breast cancer remains one of the most common forms of cancer in women.  In a small percentage of cases, the development of breast cancer is caused by inherited mutations in either BRCA1 or BRCA2, two genes whose normal function is to maintain the integrity of the genome. While inheriting a faulty BRCA gene gives women a high risk of developing cancer, only five percent of breast cancers are due to inherited gene mutations.

Mutations in BRCA1 and BRCA2 have not been found in the more common, sporadic forms of breast cancer.  Therefore scientists predicted that other genes whose products normally interact with the BRCA1 or BRCA2 proteins, and contribute to their normal function, may be more frequently altered in sporadic forms of breast cancer. This is how the Emsy gene was first identified in 2003 as a candidate gene of interest in the development of spontaneous breast cancers.

"Imagine that regulating different processes inside the cell involves systems like passing a bucket of water from a stream to a fire, from person A through D," explains Dr. Eaves. "Now imagine that individual B is the BRCA2 molecule, and it isn't doing its job properly, so a little ember can turn into a big fire. In sporadic breast cancer, we knew that BRCA2 wasn't at fault. So we asked whether changes in another molecule thought to be part of the same pathway might mimic the effects of mutations in BRCA2. Because Emsy had already been linked to BRCA2, it was an obvious culprit to test."
 
Important support for this idea first came in 2003 when Dr. David Huntsman in collaboration with colleagues in Cambridge, England discovered Emsy.  The Emsy protein interacts with BRCA2 and is overexpressed in 13 percent of sporadic breast cancers and 17 percent of ovarian cancers. 

The results now obtained by the BC Cancer Agency team provide important new evidence that alterations in Emsy may play a significant role in the formation of breast cancer. They show that the chromosomes of normal human breast cells become rapidly abnormal when there is too much of the Emsy protein present in the cells.

It was suspected that too much Emsy protein may promote cancer causing changes, says Dr. Afshin Raouf, BC Cancer Agency researcher and lead author on the Journal paper, so in order to find out, he mimicked the abnormality found in a tumour cell, and introduced unusually high amounts of Emsy to see what would happen. 

"We took Emsy out of the 'crime scene,' that is, a tumour cell, to see if it would display criminal activity when introduced into a normal cell," says Dr. Raouf. "We now have direct evidence that changes in Emsy can mimic alterations in BRCA2. This makes a strong case that changes in Emsy do contribute to the development of spontaneous forms of breast cancer."

This finding should promote further interest in determining whether Emsy may become a target for future clinical applications or diagnostic tests.

This advance is an excellent example of the progress that is facilitated by clinicians and
scientists and their trainees joining forces to tackle a difficult problem.  This work was supported by Genome Canada, the Lohn Foundation, the Canadian Institutes of Health Research, the British Columbia Breast Cancer Foundation and the Michael Smith Foundation for Health Research.

The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Research Centre conducts research into the causes and cures for cancer.

For more information, please contact:
Nicole Adams
Public Relations Officer
BC Cancer Agency
604.877.6272
nadams@bccancer.bc.ca