Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer.
A majority of breast cancers are driven by estrogen via estrogen receptor-α (ERα). Our previous studies indicate that hypoxia-inducible factor 1α (HIF-1α) cooperates with ERα in breast cancer cells. However, whether ERα is implicated in the direct regulation of HIF-1α and the role of HIF-1α in endoc...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2015
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| _version_ | 1797103233631518720 |
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| author | Yang, J AlTahan, A Jones, D Buffa, F Bridges, E Interiano, R Qu, C Vogt, N Li, J Baban, D Ragoussis, J Nicholson, R Davidoff, A Harris, A |
| author_facet | Yang, J AlTahan, A Jones, D Buffa, F Bridges, E Interiano, R Qu, C Vogt, N Li, J Baban, D Ragoussis, J Nicholson, R Davidoff, A Harris, A |
| author_sort | Yang, J |
| collection | OXFORD |
| description | A majority of breast cancers are driven by estrogen via estrogen receptor-α (ERα). Our previous studies indicate that hypoxia-inducible factor 1α (HIF-1α) cooperates with ERα in breast cancer cells. However, whether ERα is implicated in the direct regulation of HIF-1α and the role of HIF-1α in endocrine therapy response are unknown. In this study we found that a subpopulation of HIF-1α targets, many of them bearing both hypoxia response elements and estrogen response elements, are regulated by ERα in normoxia and hypoxia. Interestingly, the HIF-1α gene itself also bears an estrogen response element, and its expression is directly regulated by ERα. Clinical data revealed that expression of the HIF-1α gene or a hypoxia metagene signature is associated with a poor outcome to endocrine treatment in ERα(+) breast cancer. HIF-1α was able to confer endocrine therapy resistance to ERα(+) breast cancer cells. Our findings define, for the first time to our knowledge, a direct regulatory pathway between ERα and HIF-1α, which might modulate hormone response in treatment. |
| first_indexed | 2024-03-07T06:17:10Z |
| format | Journal article |
| id | oxford-uuid:f177b4f7-311d-4347-b1c6-feecf96e0488 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:17:10Z |
| publishDate | 2015 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:f177b4f7-311d-4347-b1c6-feecf96e04882022-03-27T11:56:15ZEstrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f177b4f7-311d-4347-b1c6-feecf96e0488EnglishSymplectic Elements at OxfordNational Academy of Sciences2015Yang, JAlTahan, AJones, DBuffa, FBridges, EInteriano, RQu, CVogt, NLi, JBaban, DRagoussis, JNicholson, RDavidoff, AHarris, AA majority of breast cancers are driven by estrogen via estrogen receptor-α (ERα). Our previous studies indicate that hypoxia-inducible factor 1α (HIF-1α) cooperates with ERα in breast cancer cells. However, whether ERα is implicated in the direct regulation of HIF-1α and the role of HIF-1α in endocrine therapy response are unknown. In this study we found that a subpopulation of HIF-1α targets, many of them bearing both hypoxia response elements and estrogen response elements, are regulated by ERα in normoxia and hypoxia. Interestingly, the HIF-1α gene itself also bears an estrogen response element, and its expression is directly regulated by ERα. Clinical data revealed that expression of the HIF-1α gene or a hypoxia metagene signature is associated with a poor outcome to endocrine treatment in ERα(+) breast cancer. HIF-1α was able to confer endocrine therapy resistance to ERα(+) breast cancer cells. Our findings define, for the first time to our knowledge, a direct regulatory pathway between ERα and HIF-1α, which might modulate hormone response in treatment. |
| spellingShingle | Yang, J AlTahan, A Jones, D Buffa, F Bridges, E Interiano, R Qu, C Vogt, N Li, J Baban, D Ragoussis, J Nicholson, R Davidoff, A Harris, A Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer. |
| title | Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer. |
| title_full | Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer. |
| title_fullStr | Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer. |
| title_full_unstemmed | Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer. |
| title_short | Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer. |
| title_sort | estrogen receptor α directly regulates the hypoxia inducible factor 1 pathway associated with antiestrogen response in breast cancer |
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