Characterization of Snail transcriptional targets in cancer Free

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The transcription factor Snail plays an important role in both embryonic development and tumor progression. It is a member of a conserved family of zinc finger proteins, which can trigger epithelial-mesenchymal transitions (EMT), promote cell invasion and protect cells from apoptosis. Although numerous roles have been proposed for Snail, the mechanisms by which Snail regulates these various cellular processes still remain largely unknown. In the present study, we have generated human SW480 colon cancer cells and human MCF-7 breast cancer cells that conditionally express human Snail. When induced in these cell lines, Snail can trigger EMT, promote cell invasion, and repress several known Snail-regulated genes, such as E-cadherin and occludin. Using an Affymetrix oligonucleotide arrays to characterize differentially expressed genes following activation of Snail expression, we have identified over 400 genes whose expression shows >2 fold change in expression. These 400 genes have been implicated in a variety of cellular processes, including cell adhesion, tight junction formation, cell proliferation and signaling, and apoptosis. Selected candidate Snail-regulated genes were validated by quantitative real-time PCR, Western blot analysis and chromatin immunoprecipitation analysis. Ongoing efforts are focused on defining the relationship between expression of Snail and candidate Snail-regulated genes in breast cancer tissues and in functional assays. Our studies will inform understanding of how Snail contributes to the cancer phenotype.