Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
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.
CitationCarcinogenesis 2006, 27 (8):1567-78
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.
- Global gene expression profiles induced by phytoestrogens in human breast cancer cells.
- Authors: Dip R, Lenz S, Antignac JP, Le Bizec B, Gmuender H, Naegeli H
- Issue date: 2008 Mar
- Comparison of the global gene expression profiles produced by methylparaben, n-butylparaben and 17beta-oestradiol in MCF7 human breast cancer cells.
- Authors: Pugazhendhi D, Sadler AJ, Darbre PD
- Issue date: 2007 Jan-Feb
- The food contaminants bisphenol A and 4-nonylphenol act as agonists for estrogen receptor alpha in MCF7 breast cancer cells.
- Authors: Vivacqua A, Recchia AG, Fasanella G, Gabriele S, Carpino A, Rago V, Di Gioia ML, Leggio A, Bonofiglio D, Liguori A, Maggiolini M
- Issue date: 2003 Dec
- Xenoestrogen action in breast cancer: impact on ER-dependent transcription and mitogenesis.
- Authors: Hess-Wilson JK, Boldison J, Weaver KE, Knudsen KE
- Issue date: 2006 Apr
- Lycopene and other carotenoids inhibit estrogenic activity of 17beta-estradiol and genistein in cancer cells.
- Authors: Hirsch K, Atzmon A, Danilenko M, Levy J, Sharoni Y
- Issue date: 2007 Aug