Monday, March 15, 2010
Fourth-year student Jeff Smith received a Breast Cancer Research Program Predoctoral Traineeship Award from the Department of Defense Congressionally Directed Medical Research Programs. This award is made based on the recipient’s talent, potential, and commitment to breast cancer research.
The focus of Jeff’s research is to gain insight into how breast cancer cells behave, especially how and why they invade and proliferate.
The Rho family of small GTPases regulates many cellular processes primarily through control of the cytoskeleton. Misregulation of Rho signaling pathways can contribute to oncogenesis through effects on cell survival, proliferation, adhesion, and invasion. Rho GTPases can only interact with downstream effector molecules after activation by specific guanine exchange factors (GEFs). To identify the GEFs involved in breast cancer progression, a siRNA was performed using the highly invasive MDA-MB-231 breast cancer cell line. Using a modified Boyden chamber assay, the Rac GEF Tiam2 was identified as a candidate regulator of invasion through matrigel. Furthermore, Tiam2 depletion resulted in a decrease in cell proliferation. Analysis of a panel of breast cancer cell lines revealed that Tiam2 expression is elevated in cells lines that harbor Ras mutations. The importance of Tiam2 expression in human breast cancer, as well as the signaling pathways important for invasion and proliferation are under continuing investigation.