KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1.
KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1.
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KDM4B 和 KDM4A 通过调节雄激素受体、c-myc 和 p27kip1 促进子宫内膜癌进展
DOI：
10.18632/oncotarget.5165
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发表时间：
2015-10-13
期刊：
影响因子：
--
通讯作者：
Bao W
中科院分区：
文献类型：
--
作者：
Qiu MT;Fan Q;Zhu Z;Kwan SY;Chen L;Chen JH;Ying ZL;Zhou Y;Gu W;Wang LH;Cheng WW;Zeng J;Wan XP;Mok SC;Wong KK;Bao W
流行病学证据表明，雄激素水平升高和与雄激素受体(AR)相关的基因变异增加了子宫内膜癌(EC)的风险。然而，AR在EC中的作用还知之甚少。我们报道了组蛋白去甲基酶KDM4家族中的两个成员是EC中AR转录活性的主要调节因子。在MFE-296细胞中，KDM4B和AR上调c-myc的表达，而在AN3CA细胞中，KDM4A和AR下调p27kip1的表达。此外，在AR高表达的EC细胞系中，KDM4B的表达与AR的表达呈正相关，而在低AR表达的EC细胞系中，KDM4A的表达与AR的表达呈正相关。在临床标本中，子宫内膜癌组织中KDM4B和KDM4A的表达均显著高于正常子宫内膜。最后，AR、KDM4B、KDM4A和c-myc基因改变的患者总体生存率和无病存活率都很低。综上所述，这些发现表明KDM4B和KDM4A通过调节AR活性促进EC进展。
Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity.