Details

Autor(en) / Beteiligte

• Yang, Jun
• AlTahan, Alaa
• Jones, Dylan T.
• Buffa, Francesca M.
• Bridges, Esther
• Interiano, Rodrigo B.
• Qu, Chunxu
• Vogt, Nathan
• Li, Ji-Liang
• Baban, Dilair
• Ragoussis, Jiannis
• Nicholson, Robert
• Davidoff, Andrew M.
• Harris, Adrian L.

Titel

Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2015-12, Vol.112 (49), p.15172-15177

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.