Identification of the Downstream Promoter Targets of Smad Tumor Suppressors in Human Breast Cancer Cells

摘要

Members of TGF-beta superfamily ligands are potent regulators of cell proliferation, differentiation and animal development. The biological effects of these ligands are mediated mainly through activation of the Smad family protein which serves as transcription factors to regulate gene expression. We analyzed the cis-regulatory elements that are responsible for conveying TGF-BETA/Activin responses at the genomic levels. Activin A and TGF- BETA transcriptional responses in immortalized normal human mammary epithelial cells were examined by gene expression profiling and computational analysis the regulatory regions of TGFbeta- responsive genes using a new algorithm, which is based on frequency of occurrence, and cross-species conservation. Our analysis revealed that a distinct set of cis-regulatory elements conserved across species is either unique or over-represented in TGF-BETA-regulated genes. A set of bioinformatics tools were developed for browsing promoters in mammalian cells.