Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Global gene expression analysis of heterotypic interactions between cancer cells and osteoblasts in vitro

ABSTRACT: Bone is the most common site of breast cancer metastasis, and this type of metastasis is a main cause of morbidity. Because breast cancer is a heterogeneous disease, the interactions between the cancer cells and the skeletal host cells, such as osteoblasts, might be diverse. Thus far, these tumor-osteoblast interactions have not yet been well characterized using a genomic approach. We hypothesized that gene expression signatures induced by tumor-osteoblast interactions might be of clinical relevance. To examine these gene expression signatures, we established an ex vivo co-culture model with benign human cells and a panel of 5 malignant breast epithelial cells in combination with primary human osteoblasts and determined associated gene expression changes using cDNA microarrays. This SuperSeries is composed of the following subset Series: GSE29030: Normal human osteoblasts and HMEC mono and coculture GSE29031: Normal human osteoblasts and Hs578t mono and coculture GSE29032: Normal human osteoblasts and MCF7 mono and coculture GSE29033: Normal human osteoblasts and MDA-MB-231 mono and coculture GSE29034: Normal human osteoblasts and SKBR3 mono and coculture GSE29035: Normal human osteoblasts and T47D mono and coculture Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Michal Rajski

PROVIDER: E-GEOD-29036 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Global gene expression analysis of the interaction between cancer cells and osteoblasts to predict bone metastasis in breast cancer.

Rajski Michal M Vogel Brigitte B Baty Florent F Rochlitz Christoph C Buess Martin M

PloS one 20120103 1

<h4>Background</h4>Bone metastasis is a main cause of morbidity in breast cancer. Since breast cancer is a heterogeneous disease, the interactions of cancer cells with the skeletal host cells might also be diverse. We hypothesized that gene expression signatures induced by heterotypic interaction of breast cancer cells and osteoblasts might be of clinical relevance.<h4>Methodology/principal findings</h4>We established an ex vivo co-culture model using benign breast epithelial cells or a panel of ...[more]

PMID: 22235336

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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

Global gene expression analysis of heterotypic interactions between cancer cells and osteoblasts in vitro

Publications

Global gene expression analysis of the interaction between cancer cells and osteoblasts to predict bone metastasis in breast cancer.

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