Maharjan Chandra K, Mo Jiao, Wang Lei, Kim Myung-Chul, Wang Sameul, Borcherding Nicholas, Vikas Praveen, Zhang Weizhou
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.
Canyonoak Consulting LLC, San Diego, CA 92127, USA.
Cancers (Basel). 2021 Dec 31;14(1):206. doi: 10.3390/cancers14010206.
The oncogenic role of estrogen receptor (ER) signaling in breast cancer has long been established. Interaction of estrogen with estrogen receptor (ER) in the nucleus activates genomic pathways of estrogen signaling. In contrast, estrogen interaction with the cell membrane-bound G-protein-coupled estrogen receptor (GPER) activates the rapid receptor-mediated signaling transduction cascades. Aberrant estrogen signaling enhances mammary epithelial cell proliferation, survival, and angiogenesis, hence is an important step towards breast cancer initiation and progression. Meanwhile, a growing number of studies also provide evidence for estrogen's pro- or anti-inflammatory roles. As other articles in this issue cover classic ER and GPER signaling mediated by estrogen, this review will discuss the crucial mechanisms by which estrogen signaling influences chronic inflammation and how that is involved in breast cancer. Xenoestrogens acquired from plant diet or exposure to industrial products constantly interact with and alter innate estrogen signaling at various levels. As such, they can modulate chronic inflammation and breast cancer development. Natural xenoestrogens generally have anti-inflammatory properties, which is consistent with their chemoprotective role in breast cancer. In contrast, synthetic xenoestrogens are proinflammatory and carcinogenic compounds that can increase the risk of breast cancer. This article also highlights important xenoestrogens with a particular focus on their role in inflammation and breast cancer. Improved understanding of the complex relationship between estrogens, inflammation, and breast cancer will guide clinical research on agents that could advance breast cancer prevention and therapy.
雌激素受体（ER）信号通路在乳腺癌中的致癌作用早已确立。雌激素与细胞核中的雌激素受体（ER）相互作用会激活雌激素信号的基因组途径。相比之下，雌激素与细胞膜结合的G蛋白偶联雌激素受体（GPER）相互作用会激活快速的受体介导的信号转导级联反应。异常的雌激素信号增强乳腺上皮细胞的增殖、存活和血管生成，因此是乳腺癌发生和发展的重要一步。与此同时，越来越多的研究也为雌激素的促炎或抗炎作用提供了证据。由于本期的其他文章涵盖了雌激素介导的经典ER和GPER信号通路，本综述将讨论雌激素信号影响慢性炎症的关键机制以及这与乳腺癌的关系。从植物性饮食或接触工业产品中获得的外源性雌激素会不断地在各个层面与内源性雌激素信号相互作用并改变它。因此，它们可以调节慢性炎症和乳腺癌的发展。天然外源性雌激素通常具有抗炎特性，这与其在乳腺癌中的化学保护作用一致。相比之下，合成外源性雌激素是促炎和致癌化合物，会增加患乳腺癌的风险。本文还重点介绍了重要的外源性雌激素，特别关注它们在炎症和乳腺癌中的作用。更好地理解雌激素、炎症和乳腺癌之间的复杂关系将指导有关可推进乳腺癌预防和治疗的药物的临床研究。
