RAS signaling in colon carcinoma: Target gene deregulation and growth control through Y-box-binding protein 1

The perturbation of the genetic program due to mutational activation of KRAS- or BRAF-mediated signal transduction is a prerequisite for the expression of neoplastic phenotypes; however, the mechanisms of cancer cell-specific transcriptional deregulation are poorly understood. We have analyzed the human colorectal cancer cell lines HCT116, HT29 and SW480 using an integrated approach combining transcriptional profiling, small molecule inhibitors targeting signaling pathway effectors, and computational prediction of regulatory elements in promoters of co-expressed genes with chromatin-based and cellular assays. We identified groups of coexpressed genes involved in similar biological processes, demonstrating a link between biological function and transcriptional organization.

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