title: AroER tri-screen™ is a novel functional assay to estimate both estrogenic and estrogen precursor activity of chemicals or biological specimens.
abstract: The purpose of the study is to define AroER tri-screen's utility for identifying endocrine-disrupting chemicals (EDCs) that target aromatase and/or estrogen receptor (ER), and to measure the total estrogenic activity in biological specimens. ER-positive, aromatase-expressing MCF-7 breast cancer cells were stably transfected with an estrogen responsive element (ERE)-driven luciferase reporter plasmid to yield a new high-throughput screening platform-the AroER tri-screen. AroER tri-screen was capable of identifying estrogen precursors, such as cortodoxone, which function as estrogens through a two-step conversion process in aromatase-expressing tissue. Furthermore, the system proved useful for assessing EDC activity in biologically relevant samples. Estimating these activities is critical because natural estrogens and estrogenic EDCs are important factors in ER-positive breast cancer risk. As our research demonstrates, incorporating functionally active aromatase into the AroER tri-screen produces a powerful and unique tool to (1) identify new EDCs targeting aromatase and/or ER; (2) discover novel EDCs activated by aromatase; and (3) estimate overall estrogenic activities in biological samples as a potential intermediate risk factor for breast cancer.
authors.affiliation: Department of Cancer Biology, Beckman Research Institute of the City of Hope, 1500 East Duarte Road, Duarte, CA, 91010, USA.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kanaya
authors.forename: Duc M
authors.initials: DM
authors.lastname: Nguyen
authors.forename: Hannah
authors.initials: H
authors.lastname: Lu
authors.forename: Yuan-Zhong
authors.initials: YZ
authors.lastname: Wang
authors.forename: Li-Yu
authors.initials: LY
authors.lastname: Hsin
authors.forename: Myrto
authors.initials: M
authors.lastname: Petreas
authors.forename: David
authors.initials: D
authors.lastname: Nelson
authors.forename: Weihong
authors.initials: W
authors.lastname: Guo
authors.forename: Peggy
authors.initials: P
authors.lastname: Reynolds
authors.forename: Tim
authors.initials: T
authors.lastname: Synold
authors.forename: Shiuan
authors.initials: S
authors.lastname: Chen
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003350:Cortodoxone / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015203:Reproducibility of Results; D014162:Transfection
chemical_list: D018931:Antineoplastic Agents, Hormonal; D052244:Endocrine Disruptors; D004967:Estrogens; D011960:Receptors, Estrogen; D003350:Cortodoxone