Hormone 'resistance' in breast cancer: the role of normal and mutant steroid receptors.
Hormone 'resistance' in breast cancer: the role of normal and mutant steroid receptors.
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乳腺癌中的激素“抵抗”：正常和突变类固醇受体的作用。
DOI：
10.1007/978-1-4615-2592-9_7
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发表时间：
1994
影响因子：
--
通讯作者：
Horwitz,KB
中科院分区：
文献类型：
--
作者：
Horwitz,KB
由于自发细胞变体的形成，遗传信息的忠实表达在肿瘤细胞中丢失。在乳腺癌中，这种演变的标志是肿瘤从依赖性肿瘤，通过肿瘤反应，到肿瘤耐药状态的进展。许多耐药肿瘤不再表达雌激素受体（ER）和孕激素受体（PR），这可能是其激素耐药性的基础。然而，所有晚期乳腺癌中有一半是受体阳性的，但它们也无法对抗雌激素治疗作出反应。标志着疾病进展的细胞异质性和表征疾病终末期的激素抗性都是长期存在的临床问题，这些问题正在慢慢地转向基础研究，这些研究集中在直接取自患者的实体瘤和源自此类肿瘤的乳腺癌细胞系上。本章讨论了突变的ER如何作为耐药性发展的一种机制。一个建议是，肿瘤细胞的亚群可以刺激，而不是抑制，抗雌激素，如他莫昔芬。我们最近的工作与正常的PR，显示条件下，孕酮拮抗剂，也可以有不适当的，激动剂样的影响，也进行了描述。这些PR模型代表了可以解释抗病毒状态的其他机制。这表明，许多“耐药”肿瘤并不是简单地忽视激素拮抗剂治疗;相反，在这些肿瘤中，激素拮抗剂已成为刺激性而不是抑制性的。
Faithful expression of genetic information is lost in tumor cells due to the formation of spontaneous cell variants. In breast cancer, this evolution is marked by progression of tumors from hormone-dependent, through hormone-responsive, to hormone-resistant states. Many resistant tumors no longer express estrogen receptors (ERs) and progesterone receptors (PRs), and this may be the basis for their hormone resistance. However, half of all advanced breast cancers are receptor positive, yet they too fail to respond to antiestrogen therapy. Both the cellular heterogeneity that mark progression of the disease and the hormone resistance that characterize the end stages of the disease have been longstanding clinical problems that are slowly yielding to basic research focused both on solid tumors taken directly from patients and on breast cancer cell lines derived from such tumors. This chapter discusses how mutant ERs serve as, one mechanism for development of resistance. A suggestion is made that subpopulations of tumor cells can be stimulated, rather than inhibited, by antiestrogens like tamoxifen. Our recent work with normal PRs, showing conditions in which progesterone antagonists, too, can have inappropriate, agonist-like effects, is also described. These PR models represent additional mechanisms that may explain the hormone-resistant state. It is suggested that many'resistant'tumors are not simply ignoring the hormone antagonist treatment; instead, in these tumors, the hormone antagonist has become stimulatory rather than inhibitory.