Darbre P D, King R J
Cellular Endocrinology Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, United Kingdom.
J Cell Biochem. 1988 Jan;36(1):83-9. doi: 10.1002/jcb.240360109.
Progression from a steroid sensitive to insensitive state is characteristic of breast tumors, but little is known about the molecular mechanisms involved. Changes in steroid receptor can be associated with the progression. This paper reviews the cell culture data pertaining to loss of response and concludes that loss of receptor is a consequence rather than a cause of insensitivity. This view is based on evidence that loss of all response parameters occurs despite the presence of fully functional receptors as determined by transfection experiments. The postreceptor defect appears to be at the level of the hormone response element of the responsive genes and may involve DNA methylation. The implications of the model for human breast cancer biology are discussed.
从类固醇敏感状态发展为不敏感状态是乳腺肿瘤的特征，但其中涉及的分子机制却鲜为人知。类固醇受体的变化可能与肿瘤进展相关。本文综述了与反应丧失相关的细胞培养数据，并得出结论：受体丧失是不敏感的结果而非原因。这一观点基于以下证据：尽管通过转染实验确定存在功能完全正常的受体，但所有反应参数仍会丧失。受体后缺陷似乎发生在反应基因的激素反应元件水平，可能涉及DNA甲基化。本文还讨论了该模型对人类乳腺癌生物学的意义。
