دورية أكاديمية
An epigenomic approach to therapy for tamoxifen-resistant breast cancer
العنوان: | An epigenomic approach to therapy for tamoxifen-resistant breast cancer |
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المؤلفون: | Feng, Qin, Zhang, Zheng, Shea, Martin J, Creighton, Chad J, Coarfa, Cristian, Hilsenbeck, Susan G, Lanz, Rainer, He, Bin, Wang, Lei, Fu, Xiaoyong, Nardone, Agostina, Song, Yongcheng, Bradner, James, Mitsiades, Nicholas, Mitsiades, Constantine S, Osborne, C Kent, Schiff, Rachel, O'Malley, Bert W |
بيانات النشر: | Nature Publishing Group |
سنة النشر: | 2014 |
المجموعة: | Harvard University: DASH - Digital Access to Scholarship at Harvard |
مصطلحات موضوعية: | epigenomic, tamoxifen, breast cancer |
الوصف: | Tamoxifen has been a frontline treatment for estrogen receptor alpha (ERα)-positive breast tumors in premenopausal women. However, resistance to tamoxifen occurs in many patients. ER still plays a critical role in the growth of breast cancer cells with acquired tamoxifen resistance, suggesting that ERα remains a valid target for treatment of tamoxifen-resistant (Tam-R) breast cancer. In an effort to identify novel regulators of ERα signaling, through a small-scale siRNA screen against histone methyl modifiers, we found WHSC1, a histone H3K36 methyltransferase, as a positive regulator of ERα signaling in breast cancer cells. We demonstrated that WHSC1 is recruited to the ERα gene by the BET protein BRD3/4, and facilitates ERα gene expression. The small-molecule BET protein inhibitor JQ1 potently suppressed the classic ERα signaling pathway and the growth of Tam-R breast cancer cells in culture. Using a Tam-R breast cancer xenograft mouse model, we demonstrated in vivo anti-breast cancer activity by JQ1 and a strong long-lasting effect of combination therapy with JQ1 and the ER degrader fulvestrant. Taken together, we provide evidence that the epigenomic proteins BRD3/4 and WHSC1 are essential regulators of estrogen receptor signaling and are novel therapeutic targets for treatment of Tam-R breast cancer. ; Version of Record |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 1001-0602 |
العلاقة: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085766/pdfTest/; Cell Research; Feng, Q., Z. Zhang, M. J. Shea, C. J. Creighton, C. Coarfa, S. G. Hilsenbeck, R. Lanz, et al. 2014. “An epigenomic approach to therapy for tamoxifen-resistant breast cancer.” Cell Research 24 (7): 809-819. doi:10.1038/cr.2014.71. http://dx.doi.org/10.1038/cr.2014.71Test.; http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717482Test |
DOI: | 10.1038/cr.2014.71 |
الإتاحة: | https://doi.org/10.1038/cr.2014.71Test http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717482Test |
رقم الانضمام: | edsbas.50520D97 |
قاعدة البيانات: | BASE |
تدمد: | 10010602 |
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DOI: | 10.1038/cr.2014.71 |