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| Status |
Public on Apr 07, 2011 |
| Title |
Complex modulation of androgen responsive gene expression by methoxyacetic acid |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Optimal androgen signaling is critical for testicular development and spermatogenesis. Methoxyacetic acid (MAA), the primary active metabolite of the industrial chemical ethylene glycol monomethyl ether, disrupts spermatogenesis and causes testicular atrophy. Transcriptional trans-activation studies have indicated that MAA can enhance androgen receptor activity, however, whether MAA actually impacts the expression of androgen-responsive genes in vivo, and which genes might be affected is not known. A mouse TM3 Leydig cell line that stably expresses androgen receptor (TM3-AR) was prepared and analyzed by transcriptional profiling to identify target gene interactions between MAA and testosterone on a global scale. MAA is shown to have widespread effects on androgen-responsive genes, affecting processes ranging from apoptosis to ion transport, cell adhesion, phosphorylation and transcription, with MAA able to enhance, as well as antagonize, androgenic responses. Moreover, testosterone is shown to exert both positive and negative effects on MAA gene responses. Motif analysis indicated that binding sites for FOX, HOX, LEF/TCF, STAT5 and MEF2 family transcription factors are among the most highly enriched in genes regulated by testosterone and MAA. Notably, 65 FOXO targets were repressed by testosterone or showed repression enhanced by MAA when combined with testosterone; these include 16 genes associated with developmental processes, six of which are Hox genes. These findings highlight the complex interactions between testosterone and MAA, and provide insight into the effects of MAA exposure on androgen-dependent processes in a Leydig cell model.
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| Overall design |
TM3-AR cells (see below) were grown in DMEM-F12 medium containing 5% horse serum and 2.5% FBS. LNCaP cells were maintained in RPMI 1640 containing 10% FBS. RNA was isolated using TRIzol reagent using the manufacturer’s protocol.
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| Contributor(s) |
Waxman DJ |
| Citation(s) |
21453523 |
| Submission date |
Feb 18, 2011 |
| Last update date |
May 10, 2018 |
| Contact name |
David J. Waxman |
| E-mail(s) |
djw@bu.edu
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| Organization name |
Boston University
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| Department |
Department of Biology and Bioinformatics Program
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| Street address |
5 Cummington Mall
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA137255 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27410_RAW.tar |
130.5 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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