Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells.

2.50
Hdl Handle:
http://hdl.handle.net/10146/68274
Title:
Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells.
Authors:
Buterin, Tonko; Koch, Caroline; Naegeli, Hanspeter
Abstract:
Estrogen 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.
Citation:
Carcinogenesis 2006, 27 (8):1567-78
Journal:
Carcinogenesis
Issue Date:
Aug-2006
URI:
http://hdl.handle.net/10146/68274
DOI:
10.1093/carcin/bgi339
PubMed ID:
16474171
Additional Links:
http://carcin.oxfordjournals.org/cgi/content/full/27/8/1567
Type:
Article
Language:
en
Description:
KEYWORDS - 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.
ISSN:
0143-3334
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
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.en
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

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