Estrogen receptor-α directly regulates the hypoxia-inducible factor 1 pathway associated with antiestrogen response in breast cancer
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- Jun Yang
- Growth Factor Group, Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom;
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- Alaa AlTahan
- Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN 38105;
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- Dylan T. Jones
- Growth Factor Group, Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom;
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- Francesca M. Buffa
- Growth Factor Group, Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom;
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- Esther Bridges
- Growth Factor Group, Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom;
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- Rodrigo B. Interiano
- Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN 38105;
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- Chunxu Qu
- Department of Bioinformatics, St. Jude Children’s Research Hospital, Memphis, TN 38105;
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- Nathan Vogt
- Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN 38105;
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- Ji-Liang Li
- Growth Factor Group, Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom;
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- Dilair Baban
- Genomics Group, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
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- Jiannis Ragoussis
- Genomics Group, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
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- Robert Nicholson
- Tenovus Centre for Cancer Research, Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3NB, United Kingdom
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- Andrew M. Davidoff
- Department of Surgery, St. Jude Children’s Research Hospital, Memphis, TN 38105;
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- Adrian L. Harris
- Growth Factor Group, Cancer Research UK, Molecular Oncology Laboratories, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom;
抄録
<jats:title>Significance</jats:title> <jats:p> About 1.7 million new cases of breast cancer occur every year, 70% of which are estrogen receptor-α (ERα) positive. Antiestrogen therapy to block ERα function is the most important approach in treatment of ERα <jats:sup>+</jats:sup> patients. However, resistance eventually will develop for various reasons. Here we demonstrate that hypoxia-inducible factor 1α (HIF-1α) is a direct transcriptional target of ERα, which may compensate for ERα function loss because many other ERα targets are also HIF-1α targets. We further show that HIF-1α is able to confer cancer cell resistance to ERα antagonists tamoxifen and fulvestrant, and the expression of HIF-1α is associated with poor survival to endocrine therapy in ERα <jats:sup>+</jats:sup> patients. Our findings thus have revealed a previously unidentified mechanism for antiestrogen resistance. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 112 (49), 15172-15177, 2015-11-23
Proceedings of the National Academy of Sciences