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| Status |
Public on Nov 06, 2017 |
| Title |
Expression profiling of MDA-MB-231 and MDA-MB-468 after ALDH1A3 manipulation, all-trans retinoic acid treatment, decitabine treatment |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Retinoids, derivatives of vitamin A, are key physiological molecules with regulatory effects on cell differentiation, proliferation and apoptosis. As a result, they are of interest for cancer therapy. Specifically, models of breast cancer have varied responses to manipulations of the retinoid signaling cascade. This study characterizes the transcriptional response of MDA-MB-231 and MDA-MB-468 breast cancer cells to retinaldehyde dehydrogenase 1A3 (ALDH1A3) and to all-trans retinoic acid (atRA). We demonstrate limited overlap between ALDH1A3-induced gene expression and atRA-induced gene expression in both cell lines, suggesting that the function of ALDH1A3 in breast cancer progression extends beyond its role as a retinaldehyde dehydrogenase. Our data reveals divergent transcriptional responses to atRA, which are largely independent of genomic retinoic acid response elements (RAREs) and consistent with the opposing responses of MDA-MB-231 and MDA-MB-468 to in vivo atRA treatment. We identify transcription factors associated with each gene set. Manipulation of one of the transcription factors (i.e. interferon regulatory factor 1; IRF1) demonstrates that it is the level of atRA-inducible and epigenetically regulated transcription factors that determine expression of target genes (e.g. CTSS, cathepsin S). This study provides a paradigm for complex, combinatorial responses of breast cancer models to atRA treatment, and illustrates the need to characterize RARE-independent responses to atRA in a variety of models.
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| Overall design |
Samples run in triplicate: MDA-MB-231 and MDA-MB-468 with or without ALDH1A3 expression; with or without atRA treatment; with or without decitabine treatment.
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| Contributor(s) |
Coyle KM, Maxwell S, Thomas ML, Marcato P |
| Citation(s) |
29192143 |
| Submission date |
Sep 04, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Paola Marcato |
| Organization name |
Dalhousie University
|
| Department |
Pathology
|
| Street address |
PO Box 15000
|
| City |
Halifax |
| State/province |
Nova Scotia |
| ZIP/Postal code |
B3H 4R2 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (48)
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| This SubSeries is part of SuperSeries: |
| GSE103427 |
Profiling of the transcriptional response to all-trans retinoic acid in breast cancer cells reveals RARE-independent mechanisms of gene expression |
|
| Relations |
| BioProject |
PRJNA401792 |
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