The presence of a protein known as Stat5 prevents laboratory-grown breast cancer cells from becoming invasive and aggressive, according to new research from Georgetown University. The research, which appears in the January 27 issue of Oncogene, could one day lead to advanced therapies for breast cancer patients.
"This new insight is significant because it is the invasive behavior of breast cancer cells that leads to the formation of metastatic cancer, the most advanced and serious form of the disease," said Hallgeir Rui, MD, PhD, associate professor of oncology, Lombardi Comprehensive Cancer Center at Georgetown University and principal investigator of the study.
The research, which was funded by the National Institutes of Health and the Department of Defense, showed that when Stat5 was active, breast cancer cells were not only less invasive, but also aggregated into clusters, resembling healthy breast cells. Conversely, loss of Stat5 stimulated invasive tumor cell activities.
"The apparent suppressive role of Stat5 in breast cancer is surprising in light of the tumor promoting role that Stat5 appears to play in leukemias, lymphomas, and prostate cancer," said Rui. "On the other hand, the new data may not be so unexpected since Stat5 is known to promote differentiation of healthy breast cells. Differentiation is a form of orderliness that is gradually lost as cancer cells become more aggressive and invasive."
Stat5 is a DNA-binding protein that regulates expression of certain genes, many of which remain unknown. During pregnancy, Stat5 is activated by the hormone prolactin, and stimulates milk production in the breast. In related research, Rui and colleagues have recently shown that Stat5 remains active in healthy breast cells in non-pregnant women. However, active Stat5 is lost in many breast cancers, especially as the tumors become more aggressive and metastatic.
Rui cautions that this research was done with cancer cells cultured in the laboratory and that additional studies are needed to determine whether Stat5 also inhibits invasion of human breast cancer cells tested in mice. These studies are underway and the outcome will determine whether new therapies could be designed to one day take advantage of the invasion-suppressive role of Stat5 in breast cancer. Because Stat5 is a protein that is located inside the cell, it cannot be administered in the form of injections to slow down breast tumor cells. However, Rui's laboratory is exploring alternative ways of switching Stat5 back on in breast cancer.
The results of this study support related research done last year by Rui and his colleagues: In a study that was published in the June 1, 2004 issue of the Journal of Clinical Oncology, the team identified Stat5 as a biomarker of a type of breast cancer that is associated with a favorable prognosis in patients. In fact, in breast cancer patients whose tumors had not yet spread to the nearby lymph nodes, loss of Stat5 was associated with a nearly 7.5-fold increased risk of death from recurring breast cancer. The new research now provides a mechanism to explain why Stat5 may be a useful tumor marker to predict risk and outcome in early stage breast cancer patients.
The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 39 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington DC area. For more information, go to http://lombardi.georgetown.edu/
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