Androgen suppresses testicular cancer cell growth in vitro and in vivo.
Androgen suppresses testicular cancer cell growth in vitro and in vivo.
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DOI：
10.18632/oncotarget.9109
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发表时间：
2016-06-07
期刊：
影响因子：
--
通讯作者：
Ukimura O
中科院分区：
文献类型：
--
作者：
Nakagawa H;Ueda T;Ito S;Shiraishi T;Taniguchi H;Kayukawa N;Nakanishi H;Ushijima S;Kanazawa M;Nakamura T;Naya Y;Hongo F;Kamoi K;Okihara K;Ukimura O
雄激素受体（AR）介导的雄激素信号传导的沉默被认为与睾丸生殖细胞肿瘤（TGCT）的发展有关。然而，雄激素/AR信号在TGCT发展中的作用尚未被研究。在这项研究中，我们证明雄激素/AR 信号在体外和体内抑制了精原细胞瘤 (SE)（一种 TGCT）的细胞生长。在体内异种移植模型中，DHT 治疗可抑制 SE 细胞的生长，而手术去势可降低雄激素水平，从而促进癌细胞生长。色氨酸羟化酶 1 (TPH1) 是血清素合成的限速酶，是 DHT 处理的 SE 细胞中表达降低的基因之一。与邻近正常组织相比，TPH1 在 SE 癌组织中高表达。 SE 细胞中雄激素/AR 信号的激活降低了 SE 细胞中 TPH1 的表达，随后细胞培养上清液中血清素的分泌减少。这些结果表明雄激素/AR信号传导的沉默可能通过TPH1基因表达水平的增加导致SE的启动和进展。
Silencing of androgen receptor (AR)-meditated androgen signaling is thought to be associated with the development of testicular germ cell tumors (TGCTs). However, the role of the androgen/AR signal in TGCT development has not been investigated. In this study, we show that the androgen/AR signal suppressed the cell growth of seminomas (SEs), a type of TGCT, in vitro and in vivo. Growth of SE cells was suppressed by DHT treatment and reduction of androgen levels by surgical castration promoted cancer cell growth in an in vivo xenograft model. Tryptophan hydroxylase 1 (TPH1), the rate limit enzyme in serotonin synthesis, was one of the genes which expression was reduced in DHT-treated SE cells. TPH1 was highly expressed in SE cancer tissues compared with adjacent normal tissues. Activation of androgen/AR signaling in SE cells reduced the expression of TPH1 in SE cells, followed by the reduction of serotonin secretion in cell culture supernatant. These results suggested that silencing of androgen/AR signaling may cause initiation and progression of SE through increase in TPH1 gene expression level.
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影响因子：
120.1
作者：
Meltzer, Herbert Y.;Dritselis, Argyris;Kirkpatrick, Peter
通讯作者：
Kirkpatrick, Peter
影响因子：
50.3
作者：
Qi J;Tripathi M;Mishra R;Sahgal N;Fazli L;Ettinger S;Placzek WJ;Claps G;Chung LW;Bowtell D;Gleave M;Bhowmick N;Ronai ZA
通讯作者：
Ronai ZA
DOI：
10.1073/pnas.0608565103
发表时间：
2006-12-12
影响因子：
11.1
作者：
Tsai, Meng-Yin;Yeh, Shauh-Der;Chang, Chawnshang
通讯作者：
Chang, Chawnshang
影响因子：
10.5
作者：
Bolton, Eric C.;So, Alex Y.;Yamamoto, Keith R.
通讯作者：
Yamamoto, Keith R.
影响因子：
14.9
作者：
Svensson C;Ceder J;Iglesias-Gato D;Chuan YC;Pang ST;Bjartell A;Martinez RM;Bott L;Helczynski L;Ulmert D;Wang Y;Niu Y;Collins C;Flores-Morales A
通讯作者：
Flores-Morales A