RHO GTPASE Involvement in Breast Cancer Migration and Invasion
Annual summary rept. 1 Mar-26 Feb 2006
HARVARD MEDICAL SCHOOL BOSTON MA
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This proposal centers on elucidating the functional role of specific candidate genes with respect to breast carcinoma invasion. Using a short hairpin RNA interference shRNA approach I have previously shown that the Rho family GTPases RhoA and RhoC both contribute to an invasive phenotype. These genes have been identified as key players regulating cellular invasion. With emerging technological advances, a single candidate gene approach is now too narrow and I have taken a more global and unbiased screening approach using small interfering RNA siRNA molecules to identify novel genes that regulate cell motility and invasion in normal MCF10A and invasive SUM-159 breast cells. This high throughput screen will also allow dissection of the up and downstream signaling components of RhoA and RhoC. Identification of genes that have conserved functions and those that have specific motility roles will be invaluable, whilst determining those that can evoke a transition from normal to a completely motile phenotype will significantly advance our studies on breast carcinoma invasion. Likewise, finding new candidates that will inhibit motility of invasive breast carcinoma cells provides more targets of direct clinical relevance. Pathway analysis is currently underway for genes that scored in the first round of screening.
- Anatomy and Physiology
- Medicine and Medical Research