Poster Sessions

CANCER-6

Leslie Rivera Rosado

L.A. Rivera Rosado, Y. Zhang, J. Rodriguez-Canales, S.Y. Moon, B. Zhang

RhoGDI Downregulation Is Associated with an Increase in Cox-2 Protein Expression and Progression of Breast Tumors

Rho GDI dissociation inhibitor (RhoGDI) is a key regulator of Rho GTPases that have been implicated in tumorigenesis and metastasis. In this study, we investigated the role of RhoGDI in breast tumor progression. Ablation of RhoGDI by RNAi interference significantly promoted tumor growth and lung metastasis of MDA-MB-231 breast cancer cells in nude mice. In RhoGDI knockdown cells, Rac1, Cdc42 and RhoA became constutively activated and translocated to membrane compartments. In addition, loss of RhoGDI significantly upregulated Cox-2 protein expression which was associated with an enhanced invasion activity of the cells. We then analyzed the expression level of RhoGDI in breast tumor specimens using a tissue array (n=208) and immunohistochemistry. The results show that RhoGDI expression inversely correlated with breast cancer progression where RhoGDI expression decreased with tumor grade and metastasis. These data suggests RhoGDI as a tumor suppressor, where its downregulation promotes tumor growth and invasion.