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The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development
dc.contributor.author | Picón Ruiz, Manuel | |
dc.contributor.author | Qureshi, Rehana | |
dc.contributor.author | Aurrekoetxea-Rodriguez, Iskander | |
dc.contributor.author | Nunes de Paiva, Vanessa | |
dc.contributor.author | D’Amico, Massimo | |
dc.contributor.author | Yoon, Hyunho | |
dc.contributor.author | Radhakrishnan, Ramya | |
dc.contributor.author | Morata-Tarifa, Cynthia | |
dc.contributor.author | Ince, Tan | |
dc.contributor.author | Lippman, Marc E. | |
dc.contributor.author | Thaller, Seth R. | |
dc.contributor.author | Rodgers, Steven E. | |
dc.contributor.author | Kesmodel, Susan | |
dc.contributor.author | Vivanco, Maria del Mar | |
dc.contributor.author | Slingerland, Joyce M. | |
dc.date.accessioned | 2022-03-24T08:04:22Z | |
dc.date.available | 2022-03-24T08:04:22Z | |
dc.date.issued | 2020-06-02 | |
dc.identifier.citation | Picón Ruiz, M. et al. The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development. Cell Metab. 2020 Jun 2;31(6):1154-1172.e9 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10481/73671 | |
dc.description.abstract | Many inflammation-associated diseases, including cancers, increase in women after menopause and with obesity. In contrast to anti-inflammatory actions of 17β-estradiol, we find estrone, which dominates after menopause, is pro-inflammatory. In human mammary adipocytes, cytokine expression increases with obesity, menopause, and cancer. Adipocyte:cancer cell interaction stimulates estrone- and NFκB-dependent pro-inflammatory cytokine upregulation. Estrone- and 17β-estradiol-driven transcriptomes differ. Estrone:ERα stimulates NFκB-mediated cytokine gene induction; 17β-estradiol opposes this. In obese mice, estrone increases and 17β-estradiol relieves inflammation. Estrone drives more rapid ER+ breast cancer growth in vivo. HSD17B14, which converts 17β-estradiol to estrone, associates with poor ER+ breast cancer outcome. Estrone and HSD17B14 upregulate inflammation, ALDH1 activity, and tumorspheres, while 17β-estradiol and HSD17B14 knockdown oppose these. Finally, a high intratumor estrone:17β-estradiol ratio increases tumor-initiating stem cells and ER+ cancer growth in vivo. These findings help explain why postmenopausal ER+ breast cancer increases with obesity, and offer new strategies for prevention and therapy. | es_ES |
dc.description.sponsorship | This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 845104 | |
dc.language.iso | eng | es_ES |
dc.rights | Atribución 3.0 España | |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | Obesity | es_ES |
dc.subject | Adipocytes | es_ES |
dc.subject | Cytokines | es_ES |
dc.subject | NFκB | es_ES |
dc.subject | Estrone | es_ES |
dc.subject | 17β-estradiol | es_ES |
dc.subject | Inflammation | es_ES |
dc.subject | ER+ breast cancer | es_ES |
dc.subject | HSD17B14 | es_ES |
dc.subject | Cancer stem cells Obesity | es_ES |
dc.title | The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | |
dc.identifier.doi | 10.1016/j.cmet.2020.05.008 | |
dc.type.hasVersion | info:eu-repo/semantics/publishedVersion | es_ES |
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