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| Status |
Public on Oct 06, 2022 |
| Title |
Hypoxia and ERα Transcriptional Crosstalk Is Associated with Endocrine Resistance in Breast Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Estrogen receptor-alpha (ERα) is the driving transcription factor in 70% of breast cancers and its activity is associated with hormone dependent tumor cell proliferation and survival. Given the recurrence of hormone resistant relapses, understanding the etiological factors fueling resistance is of major clinical interest. Hypoxia, a frequent feature of the solid tumor microenvironment, has been described to promote endocrine resistance by triggering ERα down-regulation in both in vitro and in vivo models. Yet, the consequences of hypoxia on ERα genomic activity remain largely elusive. In the present study, transcriptomic analysis shows that hypoxia regulates a fraction of ERα target genes, underlying an important regulatory overlap between hypoxic and estrogenic signaling. This gene expression reprogramming is associated with a massive reor-ganization of ERα cistrome, highlighted by a massive loss of ERα binding sites. Profiling of en-hancer acetylation revealed a hormone independent enhancer activation at the vicinity of genes harboring hypoxia inducible factor (HIFα) binding sites, the major transcription factors governing hypoxic adaptation. This activation counterbalances the loss of ERα and sustains hor-mone-independent gene expression. We describe hypoxia in luminal ERα (+) breast cancer as a key factor interfering with endocrine therapies, associated with poor clinical prognosis in breast cancer patients.
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| Overall design |
4 replicates: Control MCF7 + EtOH
4 replicates: Control MCF7 + E2
4 replicates: Hypoxic MCF7 + EtOH
4 replicates: Hypoxic MCF7 + E2
4 replicates: Rescue MCF7 + EtOH
4 replicates: Rescue MCF7 + E2
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| Contributor(s) |
Jehanno C, Le Goff P, Habauzit D, Le Page Y, Lecomte S, Lecluse E, Percevault F, Avner S, Métivier R, Michel D, Flouriot G |
| Citation(s) |
36230857 |
| Submission date |
Mar 15, 2018 |
| Last update date |
Jan 08, 2023 |
| Contact name |
Denis Habauzit |
| Organization name |
ANSES
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| Department |
TC unit
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| Street address |
10 B rue Claude Bourgelat
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| City |
Fougeres |
| ZIP/Postal code |
35306 |
| Country |
France |
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| Platforms (1) |
| GPL21185 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Probe Name Version] |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA438527 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE111914_RAW.tar |
300.8 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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