ATRA inhibits the proliferation of DU145 prostate cancer cells through reducing the methylation level of HOXB13 gene.
ATRA inhibits the proliferation of DU145 prostate cancer cells through reducing the methylation level of HOXB13 gene.
复制标题
ATRA通过降低HOXB13基因甲基化水平抑制DU145前列腺癌细胞增殖
DOI：
10.1371/journal.pone.0040943
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Huang B
中科院分区：
文献类型：
--
作者：
Liu Z;Ren G;Shangguan C;Guo L;Dong Z;Li Y;Zhang W;Zhao L;Hou P;Zhang Y;Wang X;Lu J;Huang B
全反式维甲酸（ATRA）已被广泛研究用于治疗包括前列腺癌在内的许多癌症。HOXB 13在雄激素受体阴性（AR-）前列腺癌细胞中沉默，在AR-前列腺癌细胞生长停滞中发挥作用。在这项研究中，我们打算阐明参与ATRA触发的AR-前列腺癌细胞增殖抑制的机制。我们发现ATRA能够诱导AR-前列腺癌细胞的生长停滞并增加HOXB 13的表达。EZH 2和DNMT 3b都通过涉及DNA和组蛋白甲基化修饰的表观遗传机制参与HOXB 13表达的抑制。具体地，EZH 2将DNMT 3b募集到HOXB 13启动子以形成阻遏复合物。此外，ATRA可通过降低EZH 2和DNMT 3b的表达以及减少它们与HOXB 13启动子的相互作用来上调HOXB 13。同时，HOXB 13启动子的甲基化水平在ATRA处理后降低。这项研究的结果表明，ATRA通过表观遗传修饰改变HOXB 13表达，抑制AR-抗性人前列腺癌细胞生长的新效应。
All-trans retinoic acid (ATRA) has been widely investigated for treatments of many cancers including prostate cancer. HOXB13, silenced in androgen receptor-negative (AR−) prostate cancer cells, plays a role in AR− prostate cancer cell growth arrest. In this study we intended to elucidate the mechanisms that are involved in the proliferation inhibition of AR− prostate cancer cells triggered by ATRA. We discovered that ATRA was able to induce the growth arrest and to increase HOXB13 expression in AR− prostate cancer cells. Both EZH2 and DNMT3b participated in the repression of HOXB13 expression through an epigenetic mechanism involving DNA and histone methylation modifications. Specifically, EZH2 recruited DNMT3b to HOXB13 promoter to form a repression complex. Moreover, ATRA could upregulate HOXB13 through decreasing EZH2 and DNMT3b expressions and reducing their interactions with the HOXB13 promoter. Concurrently, the methylation level of the HOXB13 promoter was reduced upon the treatment of ATRA. Results from this study implicated a novel effect of ATRA in inhibition of the growth of AR− resistant human prostate cancer cells through alteration of HOXB13 expression as a result of epigenetic modifications.
登录
查看更多内容
影响因子：
2.1
作者：
Hagiwara, Yuki;Kasukabe, Takashi;Okabe-Kado, Junko
通讯作者：
Okabe-Kado, Junko
影响因子：
8.8
作者：
Hammond, L A;Van Krinks, C H;Durham, J;Tomkins, S E;Burnett, R D;Jones, E L;Chandraratna, R A;Brown, G
通讯作者：
Brown, G
影响因子：
3.7
作者：
Fussbroich B;Wagener N;Macher-Goeppinger S;Benner A;Fälth M;Sültmann H;Holzer A;Hoppe-Seyler K;Hoppe-Seyler F
通讯作者：
Hoppe-Seyler F
影响因子：
37.3
作者：
Kim YR;Oh KJ;Park RY;Xuan NT;Kang TW;Kwon DD;Choi C;Kim MS;Nam KI;Ahn KY;Jung C
通讯作者：
Jung C
影响因子：
7.4
作者：
Lewis, MT
通讯作者：
Lewis, MT