Obiorah Ifeyinwa E, Fan Ping, Sengupta Surojeet, Jordan V Craig
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, United States.
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, United States.
Steroids. 2014 Nov;90:60-70. doi: 10.1016/j.steroids.2014.06.003. Epub 2014 Jun 11.
Antihormone therapy remains the gold standard of care in the treatment of estrogen receptor (ER) positive breast cancer. However, development of acquired long term antihormone resistance exposes a vulnerability to estrogen that induces apoptosis. Laboratory and clinical studies indicate that successful therapy with estrogens is dependent on the duration of estrogen withdrawal and menopausal status of a woman. Interrogation of estradiol (E2) induced apoptosis using molecular studies indicate treatment of long term estrogen deprived MCF-7 breast cancer cells with estrogen causes an endoplasmic reticulum stress response that induces an unfolded protein response signal to inhibit protein translation. E2 binds to the ER and mediates apoptosis through the classical genomic pathway. Furthermore, the induction of apoptosis by estrogens is dependent on the conformation of the estrogen-ER complex. In this review, we explore the mechanism and the processes involved in the paradox of estrogen induced apoptosis and the new selectivity of estrogen action on different cell populations that is correctly been deciphered for clinical practice.
抗激素疗法仍然是雌激素受体（ER）阳性乳腺癌治疗的金标准。然而，获得性长期抗激素耐药性的发展暴露出对诱导细胞凋亡的雌激素的易感性。实验室和临床研究表明，雌激素的成功治疗取决于雌激素撤药的持续时间和女性的绝经状态。使用分子研究对雌二醇（E2）诱导的细胞凋亡进行的研究表明，用雌激素治疗长期雌激素剥夺的MCF-7乳腺癌细胞会引起内质网应激反应，从而诱导未折叠蛋白反应信号来抑制蛋白质翻译。E2与ER结合并通过经典的基因组途径介导细胞凋亡。此外，雌激素诱导的细胞凋亡取决于雌激素-ER复合物的构象。在这篇综述中，我们探讨了雌激素诱导细胞凋亡的悖论所涉及的机制和过程，以及雌激素对不同细胞群体作用的新选择性，这些已被正确解读用于临床实践。
