Unknown,Transcriptomics,Genomics,Proteomics

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Responses to P. aeruginosa infection - Shapira

ABSTRACT: Synchronized C. elegans cultures were prepared using standard techniques (http://cmgm.stanford.edu/~kimlab/index_methods.html). Live young adult worms were split between NG plates pre-seeded with the non-pathogenic E. coli strain OP50 or the Pseudomonas aeruginosa clinical isolate PA14 and incubated at 25C for 4, 12 or 24 hours before harvesting. This experiment was repeated three times on independent occasions. cDNA probes were prepared from experimental samples and from reference mRNA extracted from mixed stage wild type worms grown at 25C, and were labeled with Cy3 or Cy5, respectively. In the paper corresponding to this experiment set colors were flipped for easier visualization (probes from experimental samples are represented with red, probes from reference RNA are represented with green). Groups of assays that are related as part of a time series. Infection: Exposure to the non-pathogenic E. coli strain OP50 or to the pathogenic Pseudomonas aeruginosa strain PA14 Time: Time from the beginning of exposure Michael Shapira, Brigham J. Hamlin, Jiming Rong, Karen Chen, Michal Ronen, and Man-Wah Tan , A Conserved Role for a GATA Transcription Factor in Regulating Epithelial Innate Immune Responses, Shapira et al. PNAS(in press), 2006-10-01 Computed

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: Man-Wah Tan

PROVIDER: E-GEOD-5584 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A conserved role for a GATA transcription factor in regulating epithelial innate immune responses.

Shapira Michael M Hamlin Brigham J BJ Rong Jiming J Chen Karen K Ronen Michal M Tan Man-Wah MW

Proceedings of the National Academy of Sciences of the United States of America 20060912 38

Innate immunity is an ancient and conserved defense mechanism. Although host responses toward various pathogens have been delineated, how these responses are orchestrated in a whole animal is less understood. Through an unbiased genome-wide study performed in Caenorhabditis elegans, we identified a conserved function for endodermal GATA transcription factors in regulating local epithelial innate immune responses. Gene expression and functional RNAi-based analyses identified the tissue-specific G ...[more]

PMID: 16968778

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Project description:Summary: Breast cancer cell lines have been used widely to investigate breast cancer pathobiology and new therapies. Breast cancer is a molecularly heterogeneous disease, and it is important to understand how well and which cell lines best model that diversity. In particular, microarray studies have identified molecular subtypes (luminal A, luminal B, ERBB2-associated, basal-like and normal-like) with characteristic gene-expression patterns and underlying DNA copy number alterations (CNAs). Here, we studied a collection of breast cancer cell lines to catalog molecular profiles and to assess their relation to breast cancer subtypes. Whole-genome DNA microarrays were used to profile gene expression and CNAs in a collection of 52 widely-used breast cancer cell lines, and comparisons were made to existing profiles of primary breast tumors. Hierarchical clustering was used to identify gene-expression subtypes, and Gene Set Enrichment Analysis (GSEA) to discover biological features of those subtypes. Genomic and transcriptional profiles were integrated to discover within high-amplitude CNAs candidate cancer genes with coordinately altered gene copy number and expression. Transcriptional profiling of breast cancer cell lines identified one luminal and two basal-like (A and B) subtypes. Luminal lines displayed an estrogen receptor (ER) signature and resembled luminal-A/B tumors, basal-A lines were associated with ETS-pathway and BRCA1 signatures and resembled basal-like tumors, and basal-B lines displayed mesenchymal and stem-cell characteristics. Compared to tumors, cell lines exhibited similar patterns of CNA, but an overall higher complexity of CNA (genetically simple luminal-A tumors were not represented), and only partial conservation of subtype-specific CNAs. We identified 80 high-level DNA amplifications and 13 presumptive homozygous deletions, and the resident genes with concomitantly altered gene-expression, highlighting known and novel candidate breast cancer genes. Overall, breast cancer cell lines were genetically more complex than tumors, but retained expression patterns with relevance to the luminal-basal subtype distinction. The compendium of molecular profiles defines cell lines suitable for investigations of subtype-specific pathobiology, biomarkers and therapies, and provides a resource for discovery of new breast cancer genes. HEEBO oligonucleotide microarrays from the Stanford Functional Genomics Facility were used to perform gene expression profiling of 50 human breast epithelial cell lines, in comparison to a universal RNA reference. Expression data were analyzed by hierarchical clustering to identify subgroups, and gene set enrichment analysis to identify subgroup-specific gene pathways.

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Dataset Information

Responses to P. aeruginosa infection - Shapira

Publications

A conserved role for a GATA transcription factor in regulating epithelial innate immune responses.

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