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Structural and Mole...
Structural and Molecular Mechanisms of Cytokine-Mediated Endocrine Resistance in Human Breast Cancer Cells
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- Stender, Joshua D (författare)
- Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
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- Nwachukwu, Jerome C (författare)
- Department of Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA
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- Kastrati, Irida (författare)
- Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA
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- Kim, Yohan (författare)
- Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada
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- Strid, Tobias (författare)
- Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
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- Yakir, Maayan (författare)
- Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
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- Srinivasan, Sathish (författare)
- Department of Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA
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- Nowak, Jason (författare)
- Department of Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA
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- Izard, Tina (författare)
- Department of Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA
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- Rangarajan, Erumbi S (författare)
- Department of Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA
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- Carlson, Kathryn E (författare)
- Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA
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- Katzenellenbogen, John A (författare)
- Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA
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- Yao, Xin-Qiu (författare)
- Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
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- Grant, Barry J (författare)
- Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
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- Leong, Hon S (författare)
- Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada
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- Lin, Chin-Yo (författare)
- Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA
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- Frasor, Jonna (författare)
- Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL 60612, USA
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- Nettles, Kendall W (författare)
- Department of Cancer Biology, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA
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- Glass, Christopher K (författare)
- Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA
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(creator_code:org_t)
- Cambridge, United States : Cell Press, 2017
- 2017
- Engelska.
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Ingår i: Molecular Cell. - Cambridge, United States : Cell Press. - 1097-2765 .- 1097-4164. ; 65:6, s. 1122-1135.e5
- Relaterad länk:
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http://www.cell.com/...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Human breast cancers that exhibit high proportions of immune cells and elevated levels of pro-inflammatory cytokines predict poor prognosis. Here, we demonstrate that treatment of human MCF-7 breast cancer cells with pro-inflammatory cytokines results in ERα-dependent activation of gene expression and proliferation, in the absence of ligand or presence of 4OH-tamoxifen (TOT). Cytokine activation of ERα and endocrine resistance is dependent on phosphorylation of ERα at S305 in the hinge domain. Phosphorylation of S305 by IKKβ establishes an ERα cistrome that substantially overlaps with the estradiol (E2)-dependent ERα cistrome. Structural analyses suggest that S305-P forms a charge-linked bridge with the C-terminal F domain of ERα that enables inter-domain communication and constitutive activity from the N-terminal coactivator-binding site, revealing the structural basis of endocrine resistance. ERα therefore functions as a transcriptional effector of cytokine-induced IKKβ signaling, suggesting a mechanism through which the tumor microenvironment controls tumor progression and endocrine resistance.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- breast cancer
- crystallography
- cytokines
- drug resistance
- estrogen receptor
- inflammation
- tamoxifen
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Stender, Joshua ...
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Nwachukwu, Jerom ...
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Kastrati, Irida
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Kim, Yohan
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Strid, Tobias
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Yakir, Maayan
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visa fler...
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Srinivasan, Sath ...
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Nowak, Jason
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Izard, Tina
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Rangarajan, Erum ...
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Carlson, Kathryn ...
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Katzenellenbogen ...
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Yao, Xin-Qiu
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Grant, Barry J
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Leong, Hon S
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Lin, Chin-Yo
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Frasor, Jonna
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Nettles, Kendall ...
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Glass, Christoph ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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Molecular Cell
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