Interleukin-17 receptor-like gene is a novel antiapoptotic gene highly expressed in androgen-independent prostate cancer.
Interleukin-17 receptor-like gene is a novel antiapoptotic gene highly expressed in androgen-independent prostate cancer.
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DOI：
10.1158/0008-5472.can-05-1130
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发表时间：
2006
期刊：
影响因子：
11.2
通讯作者：
Z. You;Xubao Shi;G. Duraine;Dominik R Haudenschild;C. Tepper;S. Lo;R. Gandour-Edwards;R. de Vere White-R.-d
中科院分区：
文献类型：
--
作者：
Z. You;Xubao Shi;G. Duraine;Dominik R Haudenschild;C. Tepper;S. Lo;R. Gandour-Edwards;R. de Vere White-R.-d
我们最近发现了一种新基因，白细胞介素 17 受体样 (IL-17RL)，它在正常前列腺和前列腺癌中表达。这项研究的重点是 IL-17RL 在前列腺癌中的作用。我们发现，与雄激素依赖性细胞系（LNCaP 和 MLC-SV40）和肿瘤相比，IL-17RL 在几种雄激素非依赖性前列腺癌细胞系（PC3、DU145、cds1、cds2 和 cds3）和肿瘤中的表达水平显着较高。在裸鼠体内人类前列腺肿瘤生长模型（CWR22异种移植模型）中，肿瘤中IL-17RL的表达是由雄激素剥夺诱导的。与雄激素依赖性肿瘤相比，复发的雄激素非依赖性肿瘤表达更高水平的IL-17RL。 IL-17RL 在肿瘤坏死因子 α (TNFα) 敏感的 LNCaP 细胞中过度表达，通过阻断 caspase-3 下游至 caspase-2 和 caspase-8 的激活，抑制 TNFα 诱导的细胞凋亡。相反，通过小干扰 RNA 敲低 IL-17RL 表达可诱导所有研究的前列腺癌细胞系发生细胞凋亡。综上所述，这些结果表明IL-17RL是一种新型抗凋亡基因，它可能通过促进细胞存活而部分赋予前列腺癌不依赖雄激素的生长特性。因此，IL-17RL是治疗前列腺癌的潜在治疗靶点。
We have recently identified a new gene, interleukin-17 receptor-like (IL-17RL), which is expressed in normal prostate and prostate cancer. This investigation is focused on the role of IL-17RL in prostate cancer. We found that IL-17RL was expressed at significantly higher levels in several androgen-independent prostate cancer cell lines (PC3, DU145, cds1, cds2, and cds3) and tumors compared with the androgen-dependent cell lines (LNCaP and MLC-SV40) and tumors. In an in vivo model of human prostate tumor growth in nude mice (CWR22 xenograft model), IL-17RL expression in tumors was induced by androgen deprivation. The relapsed androgen-independent tumors expressed higher levels of IL-17RL compared with the androgen-dependent tumors. Overexpression of IL-17RL in tumor necrosis factor alpha (TNFalpha)-sensitive LNCaP cells inhibited TNFalpha-induced apoptosis by blocking activation of caspase-3 downstream to caspase-2 and caspase-8. Reciprocally, knocking down IL-17RL expression by small interfering RNA induced apoptosis in all the prostate cancer cell lines studied. Taken together, these results show that IL-17RL is a novel antiapoptotic gene, which may confer partially the property of androgen-independent growth of prostate cancer by promoting cell survival. Thus, IL-17RL is a potential therapeutic target in the treatment of prostate cancer.