Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women's University, Seoul, Korea.
BMB Rep. 2011 Jul;44(7):423-34. doi: 10.5483/BMBRep.2011.44.7.423.
A female hormone, estrogen, is linked to breast cancer incidence. Estrogens undergo phase I and II metabolism by which they are biotransformed into genotoxic catechol estrogen metabolites and conjugate metabolites are produced for excretion or accumulation. The molecular mechanisms underlying estrogen-mediated mammary carcinogenesis remain unclear. Cell proliferation through activation of estrogen receptor (ER) by its agonist ligands and is clearly considered as one of carcinogenic mechanisms. Recent studies have proposed that reactive oxygen species generated from estrogen or estrogen metabolites are attributed to genotoxic effects and signal transduction through influencing redox sensitive transcription factors resulting in cell transformation, cell cycle, migration, and invasion of the breast cancer. Conjuguation metabolic pathway is thought to protect cells from genotoxic and cytotoxic effects by catechol estrogen metabolites. However, methoxylated catechol estrogens have been shown to induce ER-mediated signaling pathways, implying that conjugation is not a simply detoxification pathway. Dual action of catechol estrogen metabolites in mammary carcinogenesis as the ER-signaling molecules and chemical carcinogen will be discussed in this review.
一种女性激素，雌激素，与乳腺癌的发病率有关。雌激素通过 I 期和 II 期代谢，被生物转化为遗传毒性儿茶酚雌激素代谢物，并产生共轭代谢物进行排泄或积累。雌激素介导的乳腺癌发生的分子机制尚不清楚。通过其激动剂配体激活雌激素受体 (ER) 导致细胞增殖，这显然被认为是致癌机制之一。最近的研究表明，来自雌激素或雌激素代谢物的活性氧物种归因于遗传毒性作用和信号转导，通过影响氧化还原敏感转录因子导致细胞转化、细胞周期、迁移和乳腺癌的侵袭。共轭代谢途径被认为可以通过儿茶酚雌激素代谢物保护细胞免受遗传毒性和细胞毒性作用。然而，已经表明甲氧基儿茶酚雌激素可诱导 ER 介导的信号通路，这意味着共轭不是一种简单的解毒途径。儿茶酚雌激素代谢物在乳腺癌发生中的双重作用，作为 ER 信号分子和化学致癌物，将在本文中进行讨论。
