| Summary: | 碩士 === 國立成功大學 === 微生物暨免疫學研究所 === 87 === Abstract
RhoA, a member of Ras superfamily, plays a major role in controlling the assembly of actin stress fiber and focal adhesion. Wild type RhoA overexpression could cause morphologic changes in the medium with 10% serum but induced apoptosis in the medium with 0.2% serum. Activated Ras could also cause morphologic changes besides inducing cell transformation and proliferation. However, the roles of Ras and Rho in combination as well as their relationship in cell transformation and apoptosis remain unclear. Our transient transfection study demonstrated that dominant-negative RhoA blocked Ras related cell transformation, and mutant RhoA suppressed p21WAF-1/Cip-1 (an inhibitor of cyclin-dependent kinase). Coordinate assembly and disassembly of actin filaments drive mammalian cell migration. In our 7-4 derivatives stablely expressing dominant-negative and mutant RhoA, the cells showed slender morphology and membrane ruffling while Ras or mutant RhoA was overexpressed. Mutant RhoA blocked Ras induced apoptosis through activating NFkB and decreasing WAF-1 activity. Moreover, mutant RhoA inhibited cell migration through increase of focal adhesion. Accordingly, dominant-negative RhoA suppressed NFkB, increased WAF-1 activity therefore suppressed apoptosis. Dominant-negative RhoA also suppressed the focal adhesion and induced cell migration. In conclusion, we demonstrate that Rho is necessary for Ras transformation. Moreover, RhoA can alter cell morphology, enhances Ras transformation, suppresses cell apoptosis and controls cell migration. Nevertheless, more studies are needed in the field of the signaling pathways between Ras and RhoA. Taken together, our study on RhoA should aid in the development of novel anticancer strategies
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