Inactivation of AR activates HGF/c-Met system in human prostatic carcinoma cells
Inactivation of AR activates HGF/c-Met system in human prostatic carcinoma cells
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DOI：
10.1016/j.bbrc.2006.07.040
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发表时间：
2006-09-08
影响因子：
3.1
通讯作者：
Oyasu, Ryoichi
中科院分区：
文献类型：
--
作者：
Maeda, Akinobu;Nakashiro, Koh-ichi;Oyasu, Ryoichi
前列腺癌组织的临床研究表明，雄激素受体（AR）或c-Met过表达的改变与雄激素非依赖性进展相关。我们研究了人前列腺癌细胞中AR和c-Met信号之间的相互作用。雄激素戒断或AR特异性小干扰RNA显着降低了生长速率，而每一个动作诱导c-Met的表达。AR和c-Met表达的敲低显著抑制细胞生长。此外，芯片分析表明，c-Met的激活下调DNA修复相关基因的表达，包括8-氧代鸟嘌呤DNA糖基化酶。外源性肝细胞生长因子也可诱导细胞内活性氧的产生，导致DNA损伤的积累。这些结果表明，c-Met信号的激活可能导致自发突变或基因组不稳定的诱导，这可能导致雄激素非依赖性状态的进展。因此，c-Met信号传导用于在雄激素耗尽条件下的存活和生长。(c)2006年爱思唯尔公司All rights reserved.
Clinical studies with prostate cancer tissue indicate that alterations in androgen receptor (AR) or c-Met overexpression are associated with androgen-independent progression. We investigated the interaction between AR and c-Met signaling in human prostate cancer cells. Androgen withdrawal or AR-specific small interfering RNA significantly reduced the growth rate while each maneuver induced the expression of c-Met. Knockdown of both AR and c-Met expression markedly inhibited the cell growth. Furthermore, microarray analysis indicated that the activation of c-Met down-regulated the expression of DNA repair-related genes including 8-oxoguanine DNA glycosylase. Exogenous hepatocyte growth factor also induced the production of intracellular reactive oxygen species and resulted in the accumulation of DNA damages. These results suggested that the activation of c-Met signaling may lead to induction of spontaneous mutations or genomic instability, which may lead to the progression of androgen-independent state. Thus, c-Met signaling is utilized for survival and growth under the androgen-depleted condition. (c) 2006 Elsevier Inc. All rights reserved.