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Title:
Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivoin tumor xenografts and human breast tumors | Genome Biology
Description:
Background Estrogen plays a central role in breast cancer pathogenesis. Although many studies have characterized the estrogen regulation of genes using in vitro cell culture models by global mRNA expression profiling, it is not clear whether these genes are similarly regulated in vivo or how they might be coordinately expressed in primary human tumors. Results We generated DNA microarray-based gene expression profiles from three estrogen receptor α (ERα)-positive breast cancer cell lines stimulated by 17β-estradiol (E2) in vitro over a time course, as well as from MCF-7 cells grown as xenografts in ovariectomized athymic nude mice with E2 supplementation and after its withdrawal. When the patterns of genes regulated by E2 in vitro were compared to those obtained from xenografts, we found a remarkable overlap (over 40%) of genes regulated by E2 in both contexts. These patterns were compared to those obtained from published clinical data sets. We show that, as a group, E2-regulated genes from our preclinical models were co-expressed with ERα in a panel of ERα+ breast tumor mRNA profiles, when corrections were made for patient age, as well as with progesterone receptor. Furthermore, the E2-regulated genes were significantly enriched for transcriptional targets of the myc oncogene and were found to be coordinately expressed with Myc in human tumors. Conclusion Our results provide significant validation of a widely used in vitro model of estrogen signaling as being pathologically relevant to breast cancers in vivo.
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Keywords {🔍}
genes, expression, erα, breast, gene, tumors, estrogen, cluster, vitro, myc, cancer, tumor, dataset, figure, pubmed, cell, article, data, google, scholar, mrna, transcripts, human, vivo, cells, significant, enrichment, hours, datasets, cas, patterns, induced, profiles, correlated, profile, clusters, compared, patients, eregulated, set, high, regulated, observed, age, targets, analysis, results, time, found, xenograft,
Topics {✒️}
estrogen-induced/activator protein-1-dependent genes estrogen-receptor-negative breast cancers estrogen-receptor-positive breast cancers cross-species gene-expression analysis pgc-1alpha-responsive genes involved article download pdf article number r28 family-wise error rate phenol red-free imem dna-chip analyzer software term search results conditional myc-estrogen receptor erα-positive cell lines yellow-blue color scale sustained-released e2 pellets gene ontology consortium e2-treated breast cells age-corrected mrna expression remaining e2-inducible genes sustained-release e2 pellets e2-regulated gene signatures age-corrected er expression estrogen-regulated gene clusters authors’ original file er+/pr- breast tumors e2-induced mrna expression e2-induced gene signature estrogen receptor signaling e2-regulated gene clusters v-myb homolog considered erα-negative tumors integrated data-mining platform privacy choices/manage cookies cell cycle-related genes van de vijver identify erα-regulated genes estrogen transcription network multiple gene testing additional data files saldanha aj real-time pcr analysis estrogen-regulated gene cluster 'er/age low' group genes showing e2-regulation 'er/age low' groups transcriptional programs activated progesterone receptor valley biomedical products erα+ breast cancers identified transcription networks
Questions {❓}
- Sheikh MS, Garcia M, Pujol P, Fontana JA, Rochefort H: Why are estrogen-receptor-negative breast cancers more aggressive than the estrogen-receptor-positive breast cancers?
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headline:Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivoin tumor xenografts and human breast tumors
description:Estrogen plays a central role in breast cancer pathogenesis. Although many studies have characterized the estrogen regulation of genes using in vitro cell culture models by global mRNA expression profiling, it is not clear whether these genes are similarly regulated in vivo or how they might be coordinately expressed in primary human tumors. We generated DNA microarray-based gene expression profiles from three estrogen receptor α (ERα)-positive breast cancer cell lines stimulated by 17β-estradiol (E2) in vitro over a time course, as well as from MCF-7 cells grown as xenografts in ovariectomized athymic nude mice with E2 supplementation and after its withdrawal. When the patterns of genes regulated by E2 in vitro were compared to those obtained from xenografts, we found a remarkable overlap (over 40%) of genes regulated by E2 in both contexts. These patterns were compared to those obtained from published clinical data sets. We show that, as a group, E2-regulated genes from our preclinical models were co-expressed with ERα in a panel of ERα+ breast tumor mRNA profiles, when corrections were made for patient age, as well as with progesterone receptor. Furthermore, the E2-regulated genes were significantly enriched for transcriptional targets of the myc oncogene and were found to be coordinately expressed with Myc in human tumors. Our results provide significant validation of a widely used in vitro model of estrogen signaling as being pathologically relevant to breast cancers in vivo.
datePublished:2006-04-07T00:00:00Z
dateModified:2006-04-07T00:00:00Z
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Gene Ontology
Additional Data File
Progesterone Receptor Expression
Estrogen Signaling
Profile Dataset
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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headline:Genes regulated by estrogen in breast tumor cells in vitro are similarly regulated in vivoin tumor xenografts and human breast tumors
description:Estrogen plays a central role in breast cancer pathogenesis. Although many studies have characterized the estrogen regulation of genes using in vitro cell culture models by global mRNA expression profiling, it is not clear whether these genes are similarly regulated in vivo or how they might be coordinately expressed in primary human tumors. We generated DNA microarray-based gene expression profiles from three estrogen receptor α (ERα)-positive breast cancer cell lines stimulated by 17β-estradiol (E2) in vitro over a time course, as well as from MCF-7 cells grown as xenografts in ovariectomized athymic nude mice with E2 supplementation and after its withdrawal. When the patterns of genes regulated by E2 in vitro were compared to those obtained from xenografts, we found a remarkable overlap (over 40%) of genes regulated by E2 in both contexts. These patterns were compared to those obtained from published clinical data sets. We show that, as a group, E2-regulated genes from our preclinical models were co-expressed with ERα in a panel of ERα+ breast tumor mRNA profiles, when corrections were made for patient age, as well as with progesterone receptor. Furthermore, the E2-regulated genes were significantly enriched for transcriptional targets of the myc oncogene and were found to be coordinately expressed with Myc in human tumors. Our results provide significant validation of a widely used in vitro model of estrogen signaling as being pathologically relevant to breast cancers in vivo.
datePublished:2006-04-07T00:00:00Z
dateModified:2006-04-07T00:00:00Z
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Gene Ontology
Additional Data File
Progesterone Receptor Expression
Estrogen Signaling
Profile Dataset
Animal Genetics and Genomics
Human Genetics
Plant Genetics and Genomics
Microbial Genetics and Genomics
Bioinformatics
Evolutionary Biology
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