Using mouse models, in vivo and in vitro tests revealed that the overexpression of a cell-regulating gene called cyclin D1 may actually be advantageous for some breast cancer patients because it suppresses the activity of another gene--STAT3--which promotes cell overgrowth and prevents harmful cells from dying, explains Doris Germain, PhD, Assistant Professor of Medicine.
Dr. Samuel Waxman, the Albert A. and Vera G. List Professor of Medicine, and Clinical Professor of Medicine (Hematology and Medical Oncology) and Oncological Sciences, Yuki Ishii, PhD, the study's first author and a post-doctoral fellow in molecular oncology, and Dr. Germain, collaborated with colleagues from Mount Sinai, and researchers from the Dana-Farber Cancer Institute in Boston and the Peter MacCallum Cancer Centre in Melbourne, Australia. They found that high levels of cyclin D1 increases sensitivity to bortezomib, a recently approved FDA drug used to treat multiple myeloma. The findings indicate that cyclin D1 could be a potential biological marker to help clinicians predict which breast cancer patients would respond favorably to bortezomib.
"Tumors occur because of a lack of control over cellular division," Dr. Germain explains. "Cyclin D1 promotes cell growth so you would think it would be an advantage to the tumor. But instead, we found that when cyclin D1 is overexpressed, it blocks STAT3. So cyclin D1 is inhibiting STAT3, which in turn, keeps the cancer from developing further."
Repressing STAT3 also increased a breast tumor's sensitivity to bortezomib, adds Dr. Waxman, indicating that bortezomib may be an alternative for women whose breast cancer has high levels of cyclin D1. "Our study provides a potential explanation for the beneficial effect of cyclin D1 in breast cancer and suggests that by amplifying this effect, bortezomib may be a useful treatment," he says. "A genetic profile of a patients' breast tumors could yield a great deal of information and help clinicians create more targeted treatments for their patients."
The findings were a surprise, Dr. Waxman says, because previous studies had suggested that the overexpression of cyclin D1 was associated with a poor prognosis in other types of cancers, including pancreatic cancer. Dr. Waxman says more research is needed to ascertain which groups of women have overexpressed cyclin D1. Clinical trials could then determine whether bortezomib would benefit these patients, he adds.
Mount Sinai Press Office | EurekAlert!
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