In vitro functional characterization of genes mediating breast cancer metastasis to the brain

The aggressive behavior of tumor metastasis and the lack of effective treatments are conditions that warrant the study of basic mechanisms of metastasis. The brain is one of the sites where breast cancer often forms metastasis. A model of spontaneous breast cancer brain metastasis has been previously generated in the laboratory and a gene expression profile has been determined. From the microarray analysis a list of genes with potential clinical relevance for breast cancer metastasis to the brain has been identified, based on their correlation with reduced BMFS (Brain Metastasis-Free Survival) parameter as determined by bioinformatic analysis of breast cancer gene expression data bases. The aim of this project was to functionally characterize a subset of these up-regulated genes previously identified in genome-wide screening to mediate spontaneous experimental breast cancer metastasis to the brain, in order to understand the biological implications of these selected genes. Here we provide evidence that the Cx31 protein promotes cell proliferation, resistance to apoptosis and stem cell self-renewal potential. In addition, the EDN1 peptide provides a pro-migratory pattern, promoting effects of resistance to apoptosis and stem cell self-renewal potential. Further findings are a pro-migratory activity of CTGF and a promoting stem cell self-renewal potential of IL1R2. In short, results obtained from this project are expected to contribute to a better understanding of the mechanism of breast cancer metastasis to the brain and to identify novel therapeutic approaches