The RB tumor suppressor: a gatekeeper to hormone independence in prostate cancer?
The RB tumor suppressor: a gatekeeper to hormone independence in prostate cancer?
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DOI：
10.1172/jci45406
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发表时间：
2010-12
期刊：
影响因子：
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通讯作者：
K. Macleod
中科院分区：
文献类型：
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作者：
K. Macleod
视网膜母细胞瘤肿瘤抑制基因（RB1；编码RB）通常被认为是一个看门人，其失活-直接或间接-是肿瘤起始的限速步骤。然而，在本期的JCI中，Sharma等人表明RB1丢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是一致的。RB1的这一作用与E2F转录因子1驱动的雄激素受体（AR）上调和AR向靶基因启动子募集的增加有关。RB1在晚期癌症中的这种意想不到的功能要求我们重新评估RB1失活在其他癌症中的意义，包括其时间，疾病病因学功能以及与癌症治疗的相关性。
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.