Protein Inhibits Breast Cancer Spread

The existence of a protein called Stat5 has been shown to prevent laboratory-cultured breast cancer cells from becoming aggressive and invasive, according to a new study.

"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,” stated Hallgeir Rui, M.D., Ph.D., associate professor of oncology, Lombardi Comprehensive Cancer Center at Georgetown University (Washington, DC, USA), and lead researcher of the study.

The study, published in the January 27, 2005, issue of the journal Oncogene, demonstrated that when Stat5 was active, breast cancer cells were not only less invasive, but also gathered into clusters, resembling healthy breast cells. Conversely, the loss of Stat5 triggered invasive tumor cell activities. This new study could possibly lead to better treatments for breast cancer patients.

"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,” observed Dr. 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 binds to DNA and controls the expression of specific genes, many of which are still unknown. During pregnancy, this protein is triggered by the hormone prolactin, and triggers the production of milk in the breast. In similar studies, Dr. Rui and coworkers have demonstrated that Stat5 stays active in healthy breast cells in women who are not pregnant. Active Stat5, however, is lost in many breast cancers, particularly as the tumors become more metastatic and aggressive.

Dr. Rui warns that this study was done with cancer cells grown in the lab and that additional research is needed to determine whether this protein also inhibits invasion of human breast cells in mice. This research is ongoing and the outcome will determine whether new treatments could be created to take advantage of the invasion-suppressive role of Stat5 in breast cancer cells. Because Stat5 is a protein that is situated inside the cell, it cannot be injected to slow down breast cancer cell growth. Dr. Rui's lab, however, is assessing newer ways of turning Stat5 back on in breast cancer cells.

The present study supports earlier findings by Dr. Rui and coworkers that in patients whose tumors had not yet metastasized to the lymph nodes, loss of Stat5 was linked with an almost 7.5-fold increased risk of death from recurring cancer. This research now provides a mechanism to explain why this protein maybe a valuable tumor marker to predict risk and outcome in early-stage breast cancer patients.




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