The research published today in Cancer Research is the first to show that patients with high levels of the protein BCA2 are less likely to experience breast cancer re-occurrence than patients with low levels of BCA2.
"For the first time we have been able to show that the over-expression of BCA2 is a favorable factor in breast cancer in relation to occurrence of lymph node metastases and regional recurrence," says principle investigator Dr. Arun Seth, senior scientist in molecular and cellular biology research at Sunnybrook & Women's. "Higher levels of BCA2 are somewhat protective for regional recurrence."
Testing the effects of BCA2 expression in 1000 invasive breast tumor samples, researchers revealed that BCA2 is associated with the positive estrogen receptor, negative lymph node status and an increase in disease-free survival for regional recurrence.
Estrogen receptor (ER) positive invasive breast cancers in general have a better prognosis than ER-negative tumors and are less aggressive. In breast cancer where BCA2 and ER expression are co-regulated BCA2 might provide an alternative target for the treatment of hormone-refractory breast tumors.
BCA2, a novel RING type E3 ligase protein discovered by Seth's lab in 2000 and filed for a patent in the US in 2002, has an inherent autoubiquitination activity. Ubiquitin is a small protein that marks other proteins by attaching itself to them and directing them to the proteasome for degradation. The BCA2 mediated such ubiquitin modification of the specific cancer related proteins affect breast cancer progression.
"Now that we have determined that higher levels BCA2 are associated with a positive outcome, we are working to determine whether the BCA2 ligase functions as an oncogene in some tissues and as a tumor suppressor in others," says Seth who is also a professor at the University of Toronto. "Targeting the BCA2 mediated breakdown of tumor suppressors could provide a new therapy to block breast tumor growth."
The Canada Foundation for Innovation and the Ontario Innovation Trust, now the Ontario Research Fund - Research Infrastructure, funded the infrastructure for this research. The Canadian Institutes of Health Research and the Canadian Breast Cancer Research Alliance provided operating grants.
Sunnybrook and Women's College Health Sciences Centre is transforming health care through the dedication of its more than 10,000 staff members and volunteers. Specializing in women's health programs, caring for Canada's war veterans, conducting leading-edge research, and teaching the latest advances in healthcare through our affiliation with the University of Toronto, distinguishes Sunnybrook & Women's as one of the country's premier academic health sciences centres. Sunnybrook & Women's improves the lives of hundreds of thousands of people each year by caring for newborns, adults and the elderly, treating and preventing cancer, heart and circulation diseases, disorders of the brain, mind and nervous system, orthopaedic and arthritic conditions, and traumatic injuries.
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