The androgen receptor as an emerging target in hepatocellular carcinoma.
The androgen receptor as an emerging target in hepatocellular carcinoma.
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DOI：
10.2147/jhc.s48956
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发表时间：
2015
影响因子：
4.1
通讯作者：
Yokosuka O
中科院分区：
文献类型：
--
作者：
Kanda T;Yokosuka O
肝细胞癌（HCC）是男性主要的肝脏疾病之一，预后较差，尽管HCC的治疗在过去几十年中取得了进展。雄激素受体（AR）是核受体超家族的一员。既往研究报道，AR在人类HCC和非HCC组织中均有表达。AR的激活既依赖于配体，也不依赖于配体。后者与有丝分裂原激活的蛋白激酶-、小鼠胸腺瘤病毒癌基因同源物1 -或转录信号通路的信号换能器和激活物有关，这与HCC的发生有关。据报道，超过200种RNA表达水平被雄激素治疗改变。在肝脏中，雄激素应答基因是细胞色素p450、转化生长因子β、血管内皮生长因子和葡萄糖调节蛋白78 kDa，这些基因也与人类肝癌的发生有关。最近的研究也表明，AR在细胞迁移和转移中起作用。ar信号、内质网应激和先天免疫应答之间的相互作用可能是人类肝癌发生和HCC发展的重要因素。这一综述表明，AR可能在人类HCC中发挥潜在作用，是HCC治疗的重要靶分子之一。
Hepatocellular carcinoma (HCC) is one of the male-dominant liver diseases with poor prognosis, although treatments for HCC have been progressing in the past decades. Androgen receptor (AR) is a member of the nuclear receptor superfamily. Previous studies reported that AR was expressed in human HCC and non-HCC tissues. AR is activated both ligand-dependently and ligand-independently. The latter is associated with a mitogen-activated protein kinase–, v-akt murine thymoma viral oncogene homolog 1–, or signal-transducer and activator of transcription–signaling pathway, which has been implicated in the development of HCC. It has been reported that more than 200 RNA expression levels are altered by androgen treatment. In the liver, androgen-responsive genes are cytochrome P450s, transforming growth factor β, vascular endothelial growth factor, and glucose-regulated protein 78 kDa, which are also associated with human hepatocarcinogenesis. Recent studies also revealed that AR plays a role in cell migration and metastasis. It is possible that cross-talk among AR-signaling, endoplasmic reticulum stress, and innate immune response is important for human hepatocarcinogenesis and HCC development. This review shows that AR could play a potential role in human HCC and represent one of the important target molecules for the treatment of HCC.