| First Author | Qureshi R | Year | 2020 |
| Journal | Cell Metab | Volume | 31 |
| Issue | 6 | Pages | 1154-1172.e9 |
| PubMed ID | 32492394 | Mgi Jnum | J:296575 |
| Mgi Id | MGI:6469026 | Doi | 10.1016/j.cmet.2020.05.008 |
| Citation | Qureshi R, et al. (2020) The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development. Cell Metab 31(6):1154-1172.e9 |
| abstractText | Many inflammation-associated diseases, including cancers, increase in women after menopause and with obesity. In contrast to anti-inflammatory actions of 17beta-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 NFkappaB-dependent pro-inflammatory cytokine upregulation. Estrone- and 17beta-estradiol-driven transcriptomes differ. Estrone:ERalpha stimulates NFkappaB-mediated cytokine gene induction; 17beta-estradiol opposes this. In obese mice, estrone increases and 17beta-estradiol relieves inflammation. Estrone drives more rapid ER+ breast cancer growth in vivo. HSD17B14, which converts 17beta-estradiol to estrone, associates with poor ER+ breast cancer outcome. Estrone and HSD17B14 upregulate inflammation, ALDH1 activity, and tumorspheres, while 17beta-estradiol and HSD17B14 knockdown oppose these. Finally, a high intratumor estrone:17beta-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. |
