Isolation of Genes Involved in Rac Induced Invasion and Metastasis of Breast Carcinoma Cells
Abstract
A well-defined explanation of the progression of breast cancer to the metastatic state is still lacking at the molecular level. The involvement of Rac1, a member of the Rho GTPases, in cellular processes implicated in tumor progression, such as proliferation, adhesion and invasion, is manifest. To identify target genes of Rac1 which mediate its effects on invasion and metastasis, we applied cDNA-RDA and microarray analyses. This work resulted in the identification of 85 independent gene fragments (among them 23 novel genes) which showed altered expression levels as a result of Rac1V12 and Rac1N17 expression. The difference in mRNA abundance of twenty genes has been reconfirmed by northern blot analysis. Among the twenty genes are previously identified genes associated with tumorigenesis and/or invasion. We focused our efforts on the characterization of cyclin D1 and COX-2 (both genes' expression levels were upregulated as a result of Rac1V12 expression) with respect to mediating Rac1s effects on breast tumor progression, and found a role for COX-2 in Rac1V12-triggered increase in cell growth. In addition, we initiated experiments to obtain full-length cDNA's of the novel isolated gene fragments, which may result in the identification of novel components involved in conferring tumorigenic phenotypic changes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADB282296
Entities
People
- Linda Van Aelst
Organizations
- United States Army Medical Research and Development Command