Identification of the Downstream Promoter Targets of Smad Tumor Suppressors in Human Breast Cancer Cells
Abstract
TGF-beta is an important negative growth regulator in mammalian epithelial cells and acts to prevent tumor formation in vivo. The molecular mechanisms of tumor suppression by TGF-beta remain poorly understood. The major research goal of this proposal is to identify the downstream promoter targets of Smad tumor suppressor proteins in breast cancer cells and characterize heritable changes in tumor cells due to the deletion of Smad4 Using genomic and bioinformatic techniques. We have investigated TGF-beta signaling responses in human mammary epithelial cells using whole genome transcriptional profiling analysis coupling with a powerful and innovative bioinformatic tool developed ourselves. We utilized this new algorithm, which is based on frequency of occurrence and cross-species conservation, to search for sequence elements that may convey TGF-beta responsiveness to the target genes identified by our microarray analysis. Two regulatory elements predicted by computational analysis were further confirmed experimentally by reporter gene assays. Thus, a combination of genomic and bioinformatic approach has lead to successful identification and characterization of Smad/TGF-beta responsive elements.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA433854
Entities
People
- Xuedong Liu
Organizations
- University of Colorado Boulder