Functional Studies of Tumor Suppressor RASSF1A in Breast Cancer

摘要

This Predoctoral Traineeship Award was specially intended to support Lingyan Jiang in Functional Studies of Tumor Suppressor RASSF1A in Breast Cancer. RASSF1A is a firmly established tumor suppressor, which is silenced in a variety of cancer. Our preliminary studies demonstrate RASSF1A directly interacts with a potential oncoprotein NAP1 (nucleosome assembly protein 1) through the MTinteracting region on RASSF1A. Based on these novel findings, we hypothesized that NAP1 could play an important role in regulating RASSF1A's tumor suppressor function. By directly binding to RASSF1A, NAP1 could prevent RASSF1A from interacting with and stabilizing MTs, thus reduce RASSF1A's ability to induce cell cycle arrest and to suppress cell growth. In the first 12 months of work, I have examined NAP1-RASSF1A interaction in different phases of cell cycle. Further more, I found that purified NAP1 interferes with purified RASSF1A's ability to stabilize microtubules polymerization in vitro. Finally I have established NAP1 knock down cell lines to further study the effect of loss of endogenous NAP1 to RASSF1A's regulation on cell cycle and growth suppression. Together, work completed has prepared me for in-depth study of the role of NAP1-RASSF1A interaction in regulation of RASSF1A's tumor suppressing function.