Development of a Cellular System to Identify Modulators of B-Raf Induced Senescence in Human Fibroblasts

Abstract

Background: B-Raf is one of the earliest and most common genetic mutations observed in many different types of cancers. A single mutation in B-Raf cannot cause full-blown cancer, but may cause an observed phenotype called oncogene induced senescence (OIS). This suggests the need for cooperation between B-Raf and other genes for successful tumorigenesis.

Objective: We look to characterize Human Fibroblast cells that are able to senesce in response to elevated oncogenic expression of B-Raf.

Methods: We introduced ectopic expression of inducible B-Raf into human fibroblast cells. We characterized the successfully infected cells based on their ability to induce senescence.

Results: We isolated cells of clonal origin and we identified the clone most responsive to B-Raf expression.

Conclusions and Future Research: Our methodology proved to be effective in creating a model of B-Raf expression that can be used to study OIS. The next step is to screen the cells to identify genes that enable the cells to evade senescence. These genes could prove to be valuable chemotherapeutic targets.