Qureshi, RehanaPicon-Ruiz, ManuelAurrekoetxea-Rodriguez, IskanderNunes de Paiva, VanessaD'Amico, MassimoYoon, HyunhoRadhakrishnan, RamyaMorata-Tarifa, CynthiaInce, TanLippman, Marc EThaller, Seth RRodgers, Steven EKesmodel, SusanVivanco, Maria Del MarSlingerland, Joyce M2023-02-092023-02-092020-05-11http://hdl.handle.net/10668/15673Many 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.en17β-estradiolER+ breast cancerHSD17B14NFκBadipocytescancer stem cellscytokinesestroneinflammationobesityAnimalsBreast NeoplasmsCells, CulturedEstrogensFemaleHumansInflammationMiceMice, CongenicMice, Inbred C57BLMice, TransgenicObesityPostmenopausePremenopauseresearch article32492394open accessCélulas cultivadasEstrógenosInflamaciónNeoplasias de la mamaObesidadPosmenopausiaPremenopausiaRatones congénicosRatones endogámicos C57BLRatones transgénicos10.1016/j.cmet.2020.05.0081932-7420http://www.cell.com/article/S1550413120302473/pdf