Experimental evidence of persistent androgen-receptor-dependency in castration-resistant prostate cancer.
Experimental evidence of persistent androgen-receptor-dependency in castration-resistant prostate cancer.
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DOI：
10.3390/ijms140815615
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发表时间：
2013-07-26
影响因子：
5.6
通讯作者：
Ogawa O
中科院分区：
文献类型：
--
作者：
Kobayashi T;Inoue T;Kamba T;Ogawa O
在大多数去势抵抗前列腺癌(CRPC)中，前列腺特异性抗原(PSA)作为一种几乎完全受雄激素受体(AR)调控的基因产物，仍然作为反映疾病负担的血清标志物，表明即使在去势的血清雄激素水平下，AR信号也被激活。越来越多的证据表明，在CRPC细胞中，AR的转录能力既以配体依赖的方式激活，又以非配体依赖的方式激活。从雄激素依赖的LNCaP前列腺癌细胞衍生的一些雄激素非依赖性亚系过度表达AR和PSA，沉默AR基因会抑制细胞增殖。AR的过表达使雄激素依赖型前列腺癌细胞具有雄激素非依赖性生长能力。一些患者来源的前列腺癌异种移植株也获得了分泌PSA的去势抵抗生长能力。最近的文献表明，CRPC细胞中激活的AR调节不同于雄激素依赖状态的基因集。这一概念为新一代抗雄激素和CYP17抑制剂等抗前列腺癌新药的开发提供了非常重要的启示。
In the majority of castration-resistant prostate cancer (CRPC), prostate-specific antigen (PSA), product of a gene that is almost exclusively regulated by the androgen receptor (AR), still acts as a serum marker reflecting disease burden, indicating that AR signaling is activated even under castrate level of serum androgen. Accumulated evidence shows that transcriptional ability of AR is activated both in ligand-dependent and -independent manners in CRPC cells. Some androgen-independent sublines derived from originally androgen-dependent LNCaP prostate cancer cells overexpress the AR and PSA, for which silencing the AR gene suppresses cellular proliferation. The overexpression of the AR confers androgen-independent growth ability on androgen-dependent prostate cancer cells. Some patient-derived prostate cancer xenograft lines also acquire castration-resistant growth ability secreting PSA. More recent publications have shown that the AR activated in CRPC cells regulates distinct gene sets from that in androgen-dependent status. This concept provides very important insights in the development of novel anti-prostate cancer drugs such as new generation anti-androgens and CYP17 inhibitors.
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