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Oncogenesis:ZFHX3对ERβ抑制细胞增殖是必不可少的

2019-04-28 AlexYang MedSci原创

雌激素受体2(ESR2,也称之为ERβ)和锌指同源框3(ZFHX3,也称之为ATBF1)在小鼠中能够调控前列腺发育和抑制前列腺肿瘤的形成。ZFHX3对ESR1的功能是不可或缺的,ESR1与ESR2属于同一家族蛋白,但是在前列腺上皮中几乎不表达。ZFHX3怎样抑制前列腺致瘤过程仍旧不清楚。最近,有研究人员调查了是否ZFHX3和ERβ在抑制前列腺致瘤过程中存在互作。在C4-2B和LNCaP雄激素受体(

雌激素受体2(ESR2,也称之为ERβ)和锌指同源框3(ZFHX3,也称之为ATBF1)在小鼠中能够调控前列腺发育和抑制前列腺肿瘤的形成。ZFHX3对ESR1的功能是不可或缺的,ESR1与ESR2属于同一家族蛋白,但是在前列腺上皮中几乎不表达。ZFHX3怎样抑制前列腺致瘤过程仍旧不清楚。

最近,有研究人员调查了是否ZFHX3和ERβ在抑制前列腺致瘤过程中存在互作。在C4-2B和LNCaP雄激素受体(AR)阳性前列腺癌细胞系中,研究人员通过细胞增殖的抑制和MYC表达的抑制首次确定了ERβ的肿瘤抑制活性。研究人员发现,ZFHX3功能的缺失能够增加细胞增殖和MYC的表达,而MYC表达的下调对ZFHX3抑制细胞增殖是需要的。重要的是,ZFHX3功能丧失能够阻止ERβ对细胞增殖的作用和对MYC转录的抑制。生化角度来讲,ERβ和ZFHX3能够相互作用且占据MYC启动子的相同区域,尽管ZFHX3同样也与MYC启动子的另一个区域结合。另外,在人类前列腺组织样本中,更高水平的ZFHX3和ERβ与更好的患者生存有关。

最后,研究人员指出,他们的发现表明了ZFHX3肿瘤抑制活性的一个机制,即通过抑制MYC表达,并且在前列腺癌细胞中,ZFHX3是ERβ肿瘤抑制活性必不可少的。他们的数据同样也阐释了完整的ZFHX3功能对ERβ选择性激动剂治疗前列腺癌是需要的。

原始出处:

Qingxia Hu, Baotong Zhang, Rui Chen et al. ZFHX3 is indispensable for ERβ to inhibit cell proliferation via MYC downregulation in prostate cancer cells. Oncogenesis. 12 April 2019.

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    2020-02-16 cy0324
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    2019-04-30 zsyan
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    2019-04-30 skhzy
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    2019-04-29 AlexYang

    很好的机制解析,感谢分享!

    0

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世界范围内,前列腺癌是仅次于肺癌的男性诊断疾病。甚至是最好的诊断标准仍旧缺乏精度,导致组织检测的假阳性从而导致患者接受不必要的外科手术干预。明确的早期诊断工具的缺乏是一个很明显的问题。最近,有研究人员呈现了微流体平台,时间分辨流体力学拉伸器(TR-HS),该设备可以允许每秒内对上千个细胞的非破坏性应力进行动态的力学响应调查。TR-HS整合了高速成像和计算机视觉,从而实现悬浮于液体中单个细胞的自动化

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