Ali S, Coombes R C
CRC Laboratories, Department of Cancer Medicine, Imperial College School of Medicine, Hammersmith Hospital, London.
J Mammary Gland Biol Neoplasia. 2000 Jul;5(3):271-81. doi: 10.1023/a:1009594727358.
Estrogens have long been recognized as being important for stimulating the growth of a large proportion of breast cancers. Now it is recognized that estrogen action is mediated by two receptors, and the presence of estrogen receptor alpha (ER alpha) correlates with better prognosis and the likelihood of response to hormonal therapy. Over half of all breast cancers overexpress ER alpha and around 70% of these respond to anti-estrogen (for example tamoxifen) therapy. In addition, the presence of elevated levels of ER alpha in benign breast epithelium appears to indicate an increased risk of breast cancer, suggesting a role for ER alpha in breast cancer initiation, as well as progression. However, a proportion of ER alpha-positive tumors does not respond to endocrine therapy and the majority of those that do respond eventually become resistant. Most resistant tumors remain ER alpha-positive and frequently respond to alternative endocrine treatment, indicative of a continued role for ER alpha in breast cancer cell proliferation. The problem of resistance has resulted in the search for and the development of diverse hormonal therapies designed to inhibit ER alpha action, while research on the mechanisms which underlie resistance has shed light on the cellular mechanisms, other than ligand binding, which control ER alpha function.
长期以来，雌激素一直被认为对刺激大部分乳腺癌的生长至关重要。现在人们认识到，雌激素的作用是由两种受体介导的，雌激素受体α（ERα）的存在与较好的预后以及对激素治疗的反应可能性相关。所有乳腺癌中超过一半过度表达ERα，其中约70%对抗雌激素（如他莫昔芬）治疗有反应。此外，良性乳腺上皮中ERα水平升高似乎表明患乳腺癌的风险增加，这表明ERα在乳腺癌的发生以及进展中起作用。然而，一部分ERα阳性肿瘤对内分泌治疗无反应，而大多数有反应的肿瘤最终会产生耐药性。大多数耐药肿瘤仍为ERα阳性，并且经常对替代内分泌治疗有反应，这表明ERα在乳腺癌细胞增殖中持续发挥作用。耐药问题促使人们寻找并开发各种旨在抑制ERα作用的激素疗法，而对耐药机制的研究揭示了除配体结合外控制ERα功能的细胞机制。
