دورية أكاديمية
Embryonic transcription factor SOX9 drives breast cancer endocrine resistance.
العنوان: | Embryonic transcription factor SOX9 drives breast cancer endocrine resistance. |
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المؤلفون: | Jeselsohn, Rinath, Cornwell, MacIntosh, Pun, Matthew, Buchwalter, Gilles, Nguyen, Mai, Bango, Clyde, Huang, Ying, Kuang, Yanan, Paweletz, Cloud, Fu, Xiaoyong, Nardone, Agostina, De Angelis, Carmine, Detre, Simone, Dodson, Andrew, Mohammed, Hisham, Carroll, Jason S, Bowden, Michaela, Rao, Prakash, Long, Henry W, Li, Fugen, Dowsett, Mitchell, Schiff, Rachel, Brown, Myles |
بيانات النشر: | National Academy of Sciences //dx.doi.org/10.1073/pnas.1620993114 Proceedings of the National Academy of Sciences of the United States of America |
سنة النشر: | 2017 |
المجموعة: | Apollo - University of Cambridge Repository |
مصطلحات موضوعية: | SOX9, breast cancer, cistrome, endocrine resistance, estrogen receptor, Antineoplastic Agents, Hormonal, Breast, Breast Neoplasms, Cell Proliferation, Chromatin, Drug Resistance, Neoplasm, Epithelial-Mesenchymal Transition, Female, Humans, MCF-7 Cells, Receptors, Estrogen, SOX9 Transcription Factor, Tamoxifen |
الوصف: | The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists. |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | English |
العلاقة: | https://www.repository.cam.ac.uk/handle/1810/291901Test |
DOI: | 10.17863/CAM.39059 |
الإتاحة: | https://doi.org/10.17863/CAM.39059Test https://www.repository.cam.ac.uk/handle/1810/291901Test |
حقوق: | All rights reserved |
رقم الانضمام: | edsbas.DD1F64C1 |
قاعدة البيانات: | BASE |
DOI: | 10.17863/CAM.39059 |
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