Ben May Department for Cancer Research, Gordon Center for Integrative Sciences, University of Chicago, Chicago, Illinois, USA.
J Clin Invest. 2010 Dec;120(12):4179-82. doi: 10.1172/JCI45406. Epub 2010 Nov 22.
The retinoblastoma tumor suppressor gene (RB1; encoding RB) is often cited as a gatekeeper, whose inactivation - direct or indirect - is a rate-limiting step for tumor initiation. However, in this issue of the JCI, Sharma et al. show that RB1 loss is a late event in human prostate cancer that is coincident with the emergence of castrate-resistant metastatic disease. This role for RB1 was linked to both E2F transcription factor 1-driven upregulation of the androgen receptor (AR) and increased recruitment of the AR to target gene promoters. This unexpected function for RB1 in late-stage cancer calls upon us to reassess the significance of RB1 inactivation in other cancers in terms of its timing, function in disease etiology, and relevance for cancer therapy.
视网膜母细胞瘤肿瘤抑制基因（RB1；编码 RB）常被认为是一个“守门员”，其失活（直接或间接）是肿瘤发生的限速步骤。然而，在本期《临床研究杂志》中，Sharma 等人表明，RB1 缺失是人类前列腺癌的晚期事件，与去势抵抗性转移性疾病的出现同时发生。RB1 的这一作用与 E2F 转录因子 1 驱动的雄激素受体（AR）上调以及 AR 向靶基因启动子的募集增加有关。RB1 在晚期癌症中的这种意外作用要求我们根据其时间、在疾病发病机制中的功能以及对癌症治疗的相关性，重新评估 RB1 失活在其他癌症中的意义。
