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dc.contributor.authorButerin, Tonko
dc.contributor.authorKoch, Caroline
dc.contributor.authorNaegeli, Hanspeter
dc.date.accessioned2009-05-15T08:15:54Z
dc.date.available2009-05-15T08:15:54Z
dc.date.issued2006-08
dc.identifier.citationCarcinogenesis 2006, 27 (8):1567-78en
dc.identifier.issn0143-3334
dc.identifier.pmid16474171
dc.identifier.doi10.1093/carcin/bgi339
dc.identifier.urihttp://hdl.handle.net/10146/68274
dc.descriptionKEYWORDS - CLASSIFICATION: agonists;Antineoplastic Agents;Breast Neoplasms;Cell Line,Tumor;drug therapy;Environmental Pollutants;Estradiol;Estrogens;Estrogens,Non-Steroidal;genetics;Gene Expression Profiling;Genistein;Humans;metabolism;mechanisms of carcinogenesis;Oligonucleotide Array Sequence Analysis;pharmacology;Phenols;Polychlorinated Biphenyls;Research;Toxicology;Tumor Markers,Biological.en
dc.description.abstractEstrogen receptors display high levels of promiscuity in accommodating a wide range of ligand structures, but the functional consequence of changing receptor conformations in complex with distinct agonists is highly controversial. To determine variations in the transactivation capacity induced by different estrogenic agonists, we assessed global transcriptional profiles elicited by natural or synthetic xenoestrogens in comparison with the endogenous hormone 17beta-estradiol. Human MCF7 and T47D carcinoma cells, representing the most frequently used model systems for tumorigenic responses in the mammary gland, were synchronized by hormone starvation during 48 h. Subsequently, a 24 h exposure was carried out with equipotent concentrations of the selected xenoestrogens or 17beta-estradiol. Analysis of messenger RNA was performed on high-density oligonucleotide microarrays that display the sequences of 33,000 human transcripts, yielding a total of 181 gene products that are regulated upon estrogenic stimulation. Surprisingly, genistein (a phytoestrogen), bisphenol-A and polychlorinated biphenyl congener 54 (two synthetic xenoestrogens) produced highly congruent genomic fingerprints by regulating the same range of human genes. Also, the monotonous genomic signature observed in response to xenoestrogens is identical to the transcriptional effects induced by physiological concentrations of 17beta-estradiol. This striking functional convergence indicates that the transcription machinery is largely insensitive to the particular structure of estrogen receptor agonists. The occurrence of such converging transcriptional programs reinforces the hypothesis that multiple xenoestrogenic contaminants, of natural or anthropogenic origin, may act in conjunction with the endogenous hormone to induce additive effects in target tissues.
dc.language.isoenen
dc.relation.urlhttp://carcin.oxfordjournals.org/cgi/content/full/27/8/1567en
dc.subject.meshAntineoplastic Agents
dc.subject.meshBreast Neoplasms
dc.subject.meshCell Line, Tumor
dc.subject.meshEnvironmental Pollutants
dc.subject.meshEstradiol
dc.subject.meshEstrogens, Non-Steroidal
dc.subject.meshGene Expression Profiling
dc.subject.meshGenistein
dc.subject.meshHumans
dc.subject.meshOligonucleotide Array Sequence Analysis
dc.subject.meshPhenols
dc.subject.meshPolychlorinated Biphenyls
dc.subject.meshTumor Markers, Biological
dc.titleConvergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells.en
dc.typeArticleen
dc.identifier.journalCarcinogenesisen
html.description.abstractEstrogen receptors display high levels of promiscuity in accommodating a wide range of ligand structures, but the functional consequence of changing receptor conformations in complex with distinct agonists is highly controversial. To determine variations in the transactivation capacity induced by different estrogenic agonists, we assessed global transcriptional profiles elicited by natural or synthetic xenoestrogens in comparison with the endogenous hormone 17beta-estradiol. Human MCF7 and T47D carcinoma cells, representing the most frequently used model systems for tumorigenic responses in the mammary gland, were synchronized by hormone starvation during 48 h. Subsequently, a 24 h exposure was carried out with equipotent concentrations of the selected xenoestrogens or 17beta-estradiol. Analysis of messenger RNA was performed on high-density oligonucleotide microarrays that display the sequences of 33,000 human transcripts, yielding a total of 181 gene products that are regulated upon estrogenic stimulation. Surprisingly, genistein (a phytoestrogen), bisphenol-A and polychlorinated biphenyl congener 54 (two synthetic xenoestrogens) produced highly congruent genomic fingerprints by regulating the same range of human genes. Also, the monotonous genomic signature observed in response to xenoestrogens is identical to the transcriptional effects induced by physiological concentrations of 17beta-estradiol. This striking functional convergence indicates that the transcription machinery is largely insensitive to the particular structure of estrogen receptor agonists. The occurrence of such converging transcriptional programs reinforces the hypothesis that multiple xenoestrogenic contaminants, of natural or anthropogenic origin, may act in conjunction with the endogenous hormone to induce additive effects in target tissues.


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