title: A low-density DNA microchip for the detection of (anti-)estrogenic compounds and their relative potencies.
abstract: In the current study, a set of 12 reference compounds was tested in a low-density DNA microchip that contains probes for 11 different estrogen-responsive marker genes. Our results show that the seven most informative marker genes on the chip resulted in fingerprints that correctly predicted the (anti-)estrogenic activity of the model compounds except that of the negative control testosterone. Two marker genes, myeloid leukemia factor-1 interacting protein and ubiquitin-conjugating enzyme E2C, were even capable of correctly predicting the estrogenic potency of all five estrogen receptor (ER) agonists tested and correlated well with the potencies as determined in the MCF-7/BOS proliferation assay and the in vivo uterotrophic assay. In addition, it was demonstrated that the estrogenic responses of testosterone, both in the array tube assay and in the proliferation assay, were partially due to the conversion of testosterone into 17β-estradiol by aromatase but also due to formation of other estrogenic metabolites, the presence and estrogenic potency of which were confirmed by gas chromatography-tandem mass spectrometry analysis and a yeast-based reporter gene assay, respectively. It is concluded that low-density DNA microchip-based fingerprinting in MCF-7/BOS cells for estrogenicity marker genes provides a faster in vitro alternative to the current MCF-7/BOS cell proliferation assay (E-screen).
authors.affiliation: Division of Toxicology, Wageningen University and Research Centre, 6703 HE Wageningen, The Netherlands. si.wang@wur.nl
authors.forename: Si
authors.initials: S
authors.lastname: Wang
authors.forename: Jeroen C W
authors.initials: JC
authors.lastname: Rijk
authors.forename: Marieke J
authors.initials: MJ
authors.lastname: Pen
authors.forename: Jac M M J G
authors.initials: JM
authors.lastname: Aarts
authors.forename: Ad A C M
authors.initials: AA
authors.lastname: Peijnenburg
authors.forename: Ivonne M C M
authors.initials: IM
authors.lastname: Rietjens
authors.forename: Toine F H
authors.initials: TF
authors.lastname: Bovee
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004867:Equipment Design; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000295:instrumentation*; D053719:Tandem Mass Spectrometry
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens