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| Status |
Public on Mar 02, 2018 |
| Title |
c-Jun/AP-1 overexpression reprograms ERα signaling related to tamoxifen response in ERα-positive breast cancer [expression profiling] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
A critical mechanism that has been proposed for transcription regulation by estrogen receptor α (ER) is the tethering of ER to DNA via other transcription factors, such as AP-1. However, genome-wide assessment of the overlap in chromatin binding repertoires of these two transcription factors has not been reported. Here, we show that the AP-1 transcription factor c-Jun interacts with ER and that c-Jun chromatin binding shows extensive overlap with ER binding at the global level. Further, we show that c-Jun overexpression reprograms ER chromatin binding and modulates ER-mediated gene regulation. Our data are consistent with a mechanism where estrogen/ER-dependent crosstalk with AP-1 at the transcriptional level is mediated through the tethering of ER to DNA bound AP-1. Additionally, in our system c-Jun overexpression causes reduced sensitivity to tamoxifen in ER+ breast cancer cells. Integrated cistrome, transcriptome, and clinical data reveal TGFBI as a candidate gene which may confer tamoxifen resistance by ER and AP-1 crosstalk. Further, we show that TGFBI expression is elevated in breast cancer compared to normal breast. Together, our data provide a novel genome-wide footprint of ER and AP-1 crosstalk and suggest AP-1 and TGFBI signaling as potential therapeutic targets in AP-1-overexpressing ER-positive breast tumors.
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| Overall design |
Examination of E2 and Tamoxifen induced gene expression changes in MCF-7/c-Jun tet-off cells
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| Contributor(s) |
He H, Sinha I, Fan R, Haldosén L, Yan F, Zao C, Dahlman-Wright K |
| Citation(s) |
29467493 |
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| Submission date |
Aug 08, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Karin Dahlman-Wright |
| Organization name |
Karolinska Institutet
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| Department |
Department of Biosciences and Nutrition
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| Lab |
Medicinaren 25/Neo
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| Street address |
Blickagången 16
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| City |
Huddinge |
| ZIP/Postal code |
14157 |
| Country |
Sweden |
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| Platforms (1) |
| GPL23126 |
[Clariom_D_Human] Affymetrix Human Clariom D Assay [transcript (gene) version] |
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| Samples (18)
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| GSM2735569 |
vehicle treated MCF-7/c-Jun +Tet cells, biological rep1 |
| GSM2735570 |
vehicle treated MCF-7/c-Jun +Tet cells, biological rep2 |
| GSM2735571 |
vehicle treated MCF-7/c-Jun +Tet cells, biological rep3 |
| GSM2735572 |
vehicle treated MCF-7/c-Jun -Tet cells, biological rep1 |
| GSM2735573 |
vehicle treated MCF-7/c-Jun -Tet cells, biological rep2 |
| GSM2735574 |
vehicle treated MCF-7/c-Jun -Tet cells, biological rep3 |
| GSM2735575 |
E2 treated MCF-7/c-Jun +Tet cells, biological rep1 |
| GSM2735576 |
E2 treated MCF-7/c-Jun +Tet cells, biological rep2 |
| GSM2735577 |
E2 treated MCF-7/c-Jun +Tet cells, biological rep3 |
| GSM2735578 |
E2 treated MCF-7/c-Jun -Tet cells, biological rep1 |
| GSM2735579 |
E2 treated MCF-7/c-Jun -Tet cells, biological rep2 |
| GSM2735580 |
E2 treated MCF-7/c-Jun -Tet cells, biological rep3 |
| GSM2735581 |
Tamoxifen treated MCF-7/c-Jun +Tet cells, biological rep1 |
| GSM2735582 |
Tamoxifen treated MCF-7/c-Jun +Tet cells, biological rep2 |
| GSM2735583 |
Tamoxifen treated MCF-7/c-Jun +Tet cells, biological rep3 |
| GSM2735584 |
Tamoxifen treated MCF-7/c-Jun -Tet cells, biological rep1 |
| GSM2735585 |
Tamoxifen treated MCF-7/c-Jun -Tet cells, biological rep2 |
| GSM2735586 |
Tamoxifen treated MCF-7/c-Jun -Tet cells, biological rep3 |
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| This SubSeries is part of SuperSeries: |
| GSE102412 |
ERα and AP-1 coordinate transcription and tamoxifen response in ERα-positive breast cancer |
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| Relations |
| BioProject |
PRJNA397578 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE102367_RAW.tar |
434.2 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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