Showing papers by "Barbara J. Wold published in 2003"
TL;DR: The overabundance of p62 protein in malignant breast tissue relative to normal breast tissue is demonstrated and it is shown that PDEF stimulates the p62 promoter through at least two sites, and likely acts as a coactivator, and PSI downregulates PDEF-induced p 62 promoter activation through one of these sites.
Abstract: p62 is a multifunctional cytoplasmic protein able to noncovalently bind ubiquitin and several signaling proteins, suggesting a regulatory role connected to the ubiquitin-proteasome pathway. No studies to date have linked p62 protein expression with pathological states. Here we demonstrate the overabundance of p62 protein in malignant breast tissue relative to normal breast tissue. The proteasome inhibitor PSI increased p62 mRNA and protein; however, PSI treatment of breast epithelial cells transfected with the p62 promoter did not affect promoter activity. High levels of prostate-derived Ets factor (PDEF) mRNA have been identified in breast cancer compared to normal breast. Only the PSA and maspin promoters have been identified as targets of this transcription factor. Here we show that PDEF stimulates the p62 promoter through at least two sites, and likely acts as a coactivator. PSI treatment abrogates the PDEF-stimulated increase of p62 promoter activity by 50%. Thus, multiple mechanisms for the induction of p62 exist. We conclude that (1) p62 protein is overexpressed in breast cancer; (2) p62 mRNA and protein increase in response to PSI, with no change of basal promoter activity; (3) PDEF upregulates p62 promoter activity through at least two sites; and (4) PSI downregulates PDEF-induced p62 promoter activation through one of these sites.
169 citations
TL;DR: Cellerator describes single and multi-cellular signal transduction networks with a compact, optionally palette-driven, arrow-based notation to represent biochemical reactions and transcriptional activation.
Abstract: Cellerator describes single and multi-cellular signal transduction networks (STN) with a compact, optionally palette-driven, arrow-based notation to represent biochemical reactions and transcriptional activation. Multi-compartment systems are represented as graphs with STNs embedded in each node. Interactions include mass-action, enzymatic, allosteric and connectionist models. Reactions are translated into differential equations and can be solved numerically to generate predictive time courses or output as systems of equations that can be read by other programs. Cellerator simulations are fully extensible and portable to any operating system that supports Mathematica, and can be indefinitely nested within larger data structures to produce highly scaleable models.
135 citations
TL;DR: A clustering method based on recursive bisection is introduced for analyzing microarray gene expression data with the advantage of much improved computational efficiency while retaining effective separation of data clusters under a distance metric, a straightforward parallel implementation, and useful extraction and presentation of biological information.
10 citations