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Progestin regulation of gene expression in breast cancer and minimally transformed breast cell lines

ABSTRACT: Time course of response to synthetic progestin ORG2058 in T-47D and ZR-75-1 breast cancer cell lines and in two PR positive clones of the MCF-10A cell line: AB9 and AB32. Transcriptional response to synthetic progestin, 10nM ORG2058, was compared between the four cell lines at three treatment times.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31128 | GEO | 2012/04/26

SECONDARY ACCESSION(S): PRJNA154655

REPOSITORIES: GEO

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Progestin regulation of gene expression in breast cancer and minimally transformed breast cell lines

Project description:Time course of response to synthetic progestin ORG2058 in T-47D and ZR-75-1 breast cancer cell lines and in two PR positive clones of the MCF-10A cell line: AB9 and AB32. Transcriptional response to synthetic progestin, 10nM ORG2058, was compared between the four cell lines at three treatment times. T-47D breast cancer cells were treated in triplicate with 10nM ORG2058 or ethanol vehicle and harvested at 2, 6 and 24h after treatment for gene expression profiling

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Project description:Genome wide gene expression profiling of response to synthetic progestin ORG2058 in AB32 cells, a PR positive clone of the MCF-10A cell line, was determined after lentiviral transduction with an expression construct encoding human FOXA1. Cells were treated for 6h or 24h with 10nM ORG2058 or vehicle, 48h after transduction with the FOXA1 construct or empty vector control. Gene expression was measured in total RNA my Illumina whole genome gene expression array. Duplicate monolayer cultures of AB32 cells transduced 48h with pCDH-CMV-FOXA1-EF1-copGFP virus or negative control empty vector pCDH-CMV-mcs-EF1-copGFP virus were treated 6h or 24h with 10nM ORG2058 or 0.1% ethanol vehicle control. Cells were harvested for total RNA isolation and each sample was labelled and hybridized to a single Illumina human whole genome microarray, resulting in three replicate datasets for each of four conditions. Data were analysed separately and combined to give a mean signal intensity for each array probe.

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Project description:Major classes of hormone mimics that have been studied include environmental estrogens and androgens, but recent studies have also demonstrated the significant impacts of natural and synthetic progesterones in the environment. The objective of this study was to evaluate the molecular and physiological impacts of progestin, anti-progestin, and mixture exposures in the Eastern Mosquitofish (G. holbrooki). By comparison of gene expression profiles and modulated biological processes in the three groups, it was determined that mifepristone acts more as a progestin than as an anti-progestin, as has also been demonstrated in other species of fish. This work contributes to the overall knowledge of the impacts of this class of chemical contaminats on aquatic organisms, which are a sentinel species for pollutants as aquatic ecosystems often become a reservoir for anthropogenic contaminants.

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