Overexpression of lysine-specific demethylase 1 promotes androgen-independent transition of human prostate cancer LNCaP cells through activation of the AR signaling pathway and suppression of the p53 signaling pathway.
Overexpression of lysine-specific demethylase 1 promotes androgen-independent transition of human prostate cancer LNCaP cells through activation of the AR signaling pathway and suppression of the p53 signaling pathway.
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赖氨酸特异性去甲基酶 1 的过表达通过激活 AR 信号通路和抑制 p53 信号通路，促进人前列腺癌 LNCaP 细胞的雄激素非依赖性转变。
DOI：
10.3892/or.2015.4362
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Xing Y
中科院分区：
文献类型：
--
作者：
Song Y;Zhu H;Xiao Y;Xing Y
赖氨酸特异性去甲基酶1 （Lysine-specific demethylase 1, LSD1）是第一个被定义的组蛋白去甲基化酶，被发现与包括前列腺癌（PCa）在内的多种癌症的发生和进展密切相关。既往研究表明，LSD1与前列腺癌细胞增殖、血管生成、迁移和侵袭密切相关。然而，LSD1是否与雄激素消融条件下PCa的雄激素非依赖性（AI）转变相关仍有待阐明。本研究旨在探讨LSD1表达与人雄激素依赖性PCa LNCaP细胞AI转化的相关性。我们的数据显示，LSD1在人PCa标本和AI PCa LNCaP-AI细胞中过表达，LNCaP-AI细胞是通过在缺乏雄激素的培养基中连续培养3个月建立的。在雄激素缺失条件下，LNCaP-AI细胞生长良好，凋亡减少，G0/G1细胞周期阻滞。过表达LSD1可保护LNCaP细胞免受雄激素剥夺诱导的凋亡和G0/G1阻滞，而低表达LSD1可导致LNCaP- ai细胞更高的凋亡率和G0/G1阻滞。此外，LSD1被发现通过去甲基化调节雄激素受体（AR）和p53信号通路，从而影响细胞凋亡和细胞周期进程。这些发现表明，在雄激素消融条件下，LSD1的过表达通过激活AR信号通路和抑制p53信号通路促进了PCa LNCaP细胞的AI转化。
Lysine-specific demethylase 1 (LSD1) is the first defined histone demethylase, and was found to be closely correlated with the development and progression of various types of cancers, including prostate cancer (PCa). Previous research suggests that LSD1 is closely related with cell proliferation, angiogenesis, migration and invasion in PCa. However, it remains to be elucidated whether LSD1 is correlated with androgen-independent (AI) transition of PCa under androgen-ablated conditions. The present study aimed to investigate the correlation of LSD1 expression with AI transition of human androgen-dependent PCa LNCaP cells. Our data showed that LSD1 was overexpressed in human PCa specimens and in AI PCa LNCaP-AI cells, which were established through a three-month continuous culture of LNCaP cells in androgen-deprived medium. Under androgen-deprived conditions, LNCaP-AI cells grew perfectly with less apoptosis and G0/G1 cell cycle arrest. Overexpression of LSD1 protected the LNCaP cells from androgen deprivation-induced apoptosis and G0/G1 arrest, while knockdown of LSD1 drove LNCaP-AI cells into a higher rate of apoptosis and G0/G1 arrest. Furthermore, LSD1 was found to regulate the androgen receptor (AR) and p53 signaling pathways via demethylation, subsequently influencing apoptosis and cell cycle progression. These findings revealed that overexpression of LSD1 promoted AI transition of PCa LNCaP cells under androgen-ablated conditions via activation of the AR signaling pathway and suppression of the p53 signaling pathway.
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影响因子：
3.7
作者：
Nagasawa S;Sedukhina AS;Nakagawa Y;Maeda I;Kubota M;Ohnuma S;Tsugawa K;Ohta T;Roche-Molina M;Bernal JA;Narváez AJ;Jeyasekharan AD;Sato K
通讯作者：
Sato K
影响因子：
6.4
作者：
Willmann, Dominica;Lim, Soyoung;Buettner, Reinhard
通讯作者：
Buettner, Reinhard
影响因子：
--
作者：
Ramamurthy VP;Ramalingam S;Gediya L;Kwegyir-Afful AK;Njar VC
通讯作者：
Njar VC
DOI：
10.1038/ncpuro1296
发表时间：
2009-02
期刊：
NATURE CLINICAL PRACTICE UROLOGY
影响因子：
--
作者：
Harris, William P.;Mostaghel, Elahe A.;Nelson, Peter S.;Montgomery, Bruce
通讯作者：
Montgomery, Bruce
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin