Isolation of Genes in Rac Induced Invasion and Metastasis of Breast Carcinoma Cells

摘要

A better understanding of the progression of a primary breast tumor to its metastatic state is crucial to develop more direct forms of screenings and therapy. Members of the Rho GTPases, in particular Rac1, play important roles in cellular processes implicated in tumor progression, such as proliferation, adhesion and invasion. To identify target genes of RacI which mediate its effects on the above processes, we applied cDNA-RDA and microarray analyses. These experiments resulted in the identification of 85 independent gene fragments (among them 23 novel genes) which showed altered expression levels as a result of RacIV12 and RacIN17 expression. The difference in mRNA abundance of twenty genes has been reconfirmed by northern blot analysis. Among them are previously identified genes associated with tumorigenesis andlor invasion, such as cyclin D1, COX-2, CDO, ICAP1 and NF-kappa B. We focussed our efforts on the characterization of cyclin Dl, COX-2 and more recently ICAP1 with respect to mediating RacIV12 effect on cell proliferation and invasion. We obtained evidence supporting a role for COX-2 in RacIV12-triggered increase in cell growth. The further characterization of the other cDNAs is likely to identify additional relevant RacI targets and is presently ongoing.