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Welcome to the website companion to Gene Expression Patterns Associated with p53 Status in Breast Cancer (Submitted) Melissa A. Troester1*, Jason I. Herschkowitz2, Daniel S. Oh2, Xiaping He1,3, Katherine A. Hoadley2, and Charles M. Perou1,3,4*. 1Lineberger Comprehensive Cancer Center, 2Curriculum in Genetics and Molecular Biology, 3Department of Genetics, 4Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill. Abstract Breast cancer subtypes identified in genomic studies have different underlying genetic defects. Mutations in the tumor suppressor p53 occur more frequently in estrogen receptor (ER) negative, basal-like and HER2-amplified tumors than in luminal, ER positive tumors. Thus, because p53 mutation status is tightly linked to other characteristics of prognostic importance, it is difficult to identify p53’s independent prognostic effects. The relation between p53 status and subtype can be better studied by combining data from primary tumors with data from isogenic cell line pairs (with and without p53 function). In this study, the p53-dependent gene expression signatures of four cell lines (MCF-7, ZR-75-1, and two immortalized human mammary epithelial cell lines) were identified by comparing p53-RNAi transduced cell lines to their parent cell lines. Cell lines were treated with vehicle only or doxorubicin to identify p53 responses in both non-induced and induced states. Each cell line displayed distinct patterns of p53-dependent gene expression, but cell type specific (basal vs. luminal) commonalities were evident. Further, a common gene expression signature associated with p53 loss across all four cell lines was identified. This signature showed overlap with the signature of p53 loss in primary breast tumors. To validate the biological relevance of the common p53 loss signature, we demonstrated that this gene set predicted relapse-free, disease-specific, and overall survival in independent test data. A list of significantly expressed genes Full Text Online
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