美国乔治城大学Joyce M. Slingerland、西尔维斯特综合癌症中心Rehana Qureshi、Manuel Picon-Ruiz等研究人员合作发现，绝经前后的主要雌激素在肥胖驱动的乳腺炎症和乳腺癌发展中起相反作用。该项研究成果发表在2020年6月2日出版的《细胞—代谢》杂志上。

Title: The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development

Author: Rehana Qureshi, Manuel Picon-Ruiz, Iskander Aurrekoetxea-Rodriguez, Vanessa Nunes de Paiva, Massimo D’Amico, Hyunho Yoon, Ramya Radhakrishnan, Cynthia Morata-Tarifa, Tan Ince, Marc E. Lippman, Seth R. Thaller, Steven E. Rodgers, Susan Kesmodel, Maria del Mar Vivanco, Joyce M. Slingerland

Issue&Volume: 2020/06/02

Abstract: Many inflammation-associated diseases, including cancers, increase in women aftermenopause and with obesity. In contrast to anti-inflammatory actions of 17β-estradiol,we find estrone, which dominates after menopause, is pro-inflammatory. In human mammaryadipocytes, cytokine expression increases with obesity, menopause, and cancer. Adipocyte:cancercell interaction stimulates estrone- and NFκB-dependent pro-inflammatory cytokineupregulation. Estrone- and 17β-estradiol-driven transcriptomes differ. Estrone:ERαstimulates NFκB-mediated cytokine gene induction; 17β-estradiol opposes this. In obesemice, estrone increases and 17β-estradiol relieves inflammation. Estrone drives morerapid ER+ breast cancer growth in vivo. HSD17B14, which converts 17β-estradiol to estrone, associates with poor ER+ breastcancer outcome. Estrone and HSD17B14 upregulate inflammation, ALDH1 activity, andtumorspheres, while 17β-estradiol and HSD17B14 knockdown oppose these. Finally, a high intratumor estrone:17β-estradiol ratio increasestumor-initiating stem cells and ER+ cancer growth in vivo. These findings help explain why postmenopausal ER+ breast cancer increases withobesity, and offer new strategies for prevention and therapy.

DOI: 10.1016/j.cmet.2020.05.008

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30247-3