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Gene expression profiling of MCF7 breast cancer xenografts overexpressing podoplanin

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

OTHER RELATED OMICS DATASETS IN: PRJNA114391PRJNA114509PRJNA111731

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE14552 | GEO | 2010/05/25

SECONDARY ACCESSION(S): PRJNA111731

REPOSITORIES: GEO

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Gene expression profiling of MCF7 breast cancer xenografts overexpressing podoplanin (human array)

Project description:Expression of the membrane glycoprotein podoplanin is upregulated in several human cancers and might be associated with their malignant progression. The exact biological function and molecular targets of cancer cell-expressed podoplanin have remained unclear, however. Here, we ectopically overexpressed podoplanin in a human breast carcinoma xenograft model to study its role in cancer progression. To identify molecular mediators of podoplanin-induced effects we compared transcriptional profiles of podoplanin-overexpressing and control tumors. Keywords: comparative transcriptional profiling

2010-05-25 | GSE14550 | GEO

Gene expression profiling of tumor stroma of MCF7 breast cancer xenografts overexpressing podoplanin (mouse array)

Project description:Expression of the membrane glycoprotein podoplanin is upregulated in several human cancers and might be associated with their malignant progression. The exact biological function and molecular targets of cancer cell-expressed podoplanin have remained unclear, however. Here, we ectopically overexpressed podoplanin in a human breast carcinoma xenograft model to study its role in cancer progression. To identify potential molecular mediators of podoplanin-induced effects in the murine tumor stroma we compared transcriptional profiles of podoplanin-overexpressing and control tumors using mouse microarrays. Keywords: comparative transcriptional profiling

2010-05-25 | GSE14551 | GEO

Gene expression profiling of MCF7 breast cancer xenografts overexpressing podoplanin (human array)

Project description:Gene expression profiling of MCF7 breast cancer xenografts overexpressing podoplanin (human array)

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Gene expression profiling of tumor stroma of MCF7 breast cancer xenografts overexpressing podoplanin (mouse array)

Project description:Gene expression profiling of tumor stroma of MCF7 breast cancer xenografts overexpressing podoplanin (mouse array)

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Patient-derived luminal breast cancer xenografts with progestins

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The Angiogenic Secretome in VEGF overexpressing Breast Cancer Xenografts.

Project description:The plasticity of cancer cells and the fluidity of the tumor microenvironment continue to present major challenges in the comprehensive understanding of cancer that is essential to design effective treatments. The tumor interstitial fluid (TIF) encompasses the secretome and holds the key to several of the phenotypic characteristics of cancer. Difficulties in sampling this fluid have resulted in limited characterization of its components. Here we have sampled TIF from triple negative and estrogen receptor (ER)-positive human breast tumor xenografts with or without VEGF overexpression. Angiogenesis-related factors were characterized in the TIF and plasma, to understand the relationship between the TIF and plasma secretomes. Clear differences were observed between the TIF and plasma angiogenic secretomes in triple negative MDA-MB-231 breast cancer xenografts compared to ER-positive MCF-7 xenografts with or without VEGF overexpression that provide new insights into TIF components and the role of VEGF in modifying the angiogenic secretome.

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Transcription profiling of mouse MCF7 wt xenografts

Project description:To investigate molecular mechanisms of resistance, we used two different in vivo xenograft models of estrogen receptor-positive (ER+) breast cancer, with or without HER2 over-expression (MCF7/HER2-18 and MCF7 wt, respectively). Mice with established tumors were assigned to the following treatment groups: continued estrogen supplementation (E2), estrogen deprivation (ED), ED plus tamoxifen (Tam), all with or without the EGFR tyrosine kinase inhibitor gefinitinib (G). Another group received ED plus the antiestrogen fulvestrant (MCF7 wt only). Tumors with acquired or de novo resistance to these endocrine therapies were profiled for mRNA expression using Affymetrix Genechip arrays. Experiment Overall Design: MCF7 xenografts were established in ovariectomized five to six week-old nu/nu athymic nude mice supplemented with 0.25 mg 21 day release estrogen pellets by inoculating subcutaneously (s.c.) 5E-6 cells. When tumors reached the size of 150-200 mm3 (3-5 weeks), the animals were randomly allocated to continued estrogen (E2), continued estrogen with gefitinib (E2+G; 100mg/kg, 5 days/week), estrogen withdrawal alone (ED; by removal of the estrogen pellets), and estrogen withdrawal plus tamoxifen citrate (Tam; 500 microg/animal s.c. in peanut oil, 5 days/week), with either gefitinib (Tam+G; 100mg/kg, 5 days/week) or vehicle (1% Tween 80) administered via gavage, as well as estrogen withdrawal plus fulvestrant (ICI 182,780) in the MCF7 wt model (Fulv; 5mg/mouse s.c. once weekly), and estrogen withdrawal with gefitinib (ED+G). Tumors were harvested for molecular studies when they became resistant to treatment and reached the size of 1000 mm3 (n=7).

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Molecular profiling of patient-derived breast cancer xenografts.

Project description:INTRODUCTION: Identification of new therapeutic agents for breast cancer (BC) requires preclinical models that reproduce the molecular characteristics of their respective clinical tumors. In this work, we analyzed the genomic and gene expression profiles of human BC xenografts and the corresponding patient tumors. METHODS: Eighteen BC xenografts were obtained by grafting tumor fragments from patients into Swiss nude mice. Molecular characterization of patient tumors and xenografts was performed by DNA copy number analysis and gene expression analysis using Affymetrix Microarrays. RESULTS: Comparison analysis showed that 14/18 pairs of tumors shared more than 56% of copy number alterations (CNA). Unsupervised hierarchical clustering analysis showed that 16/18 pairs segregated together, confirming the similarity between tumor pairs. Analysis of recurrent CNA changes between patient tumors and xenografts showed losses in 176 chromosomal regions and gains in 202 chromosomal regions. Gene expression profile analysis showed that less than 5% of genes had recurrent variations between patient tumors and their respective xenografts; these genes largely corresponded to human stromal compartment genes. Finally, analysis of different passages of the same tumor showed that sequential mouse-to-mouse tumor grafts did not affect genomic rearrangements or gene expression profiles, suggesting genetic stability of these models over time. CONCLUSIONS: This panel of human BC xenografts maintains the overall genomic and gene expression profile of the corresponding patient tumors and remains stable throughout sequential in vivo generations. The observed genomic profile and gene expression differences appear to be due to the loss of human stromal genes. These xenografts, therefore, represent a validated model for preclinical investigation of new therapeutic agents.

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Expression data from MCF7 wt and MCF7/HER2-18 xenografts

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