"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.