@misc{10481/73671,
year = {2020},
month = {6},
url = {http://hdl.handle.net/10481/73671},
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.},
organization = {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},
keywords = {Obesity},
keywords = {Adipocytes},
keywords = {Cytokines},
keywords = {NFκB},
keywords = {Estrone},
keywords = {17β-estradiol},
keywords = {Inflammation},
keywords = {ER+ breast cancer},
keywords = {HSD17B14},
keywords = {Cancer stem cells Obesity},
title = {The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development},
doi = {10.1016/j.cmet.2020.05.008},
author = {Picón Ruiz, Manuel and Qureshi, Rehana and Aurrekoetxea-Rodriguez, Iskander and Nunes de Paiva, Vanessa and D’Amico, Massimo and Yoon, Hyunho and Radhakrishnan, Ramya and Morata-Tarifa, Cynthia and Ince, Tan and Lippman, Marc E. and Thaller, Seth R. and Rodgers, Steven E. and Kesmodel, Susan and Vivanco, Maria del Mar and Slingerland, Joyce M.},
}