Brit J Cancer:精液凝固蛋白I与雄激素受体互作分析

2017-12-02 AlexYang MedSci原创

之前,有研究人员阐释了一种精浆蛋白-精液凝固蛋白I(SgI)能够作为一种雄激素受体(AR)共激活剂起作用。同时,在AR共调节因子中的一些短序列基序,比如LxxLL(L=亮氨酸),展现出了与AR特异性的互作关系。最近,有研究人员在体外试验前列腺癌系列中,调查了SgI中LxxLL基序在于AR和细胞生长互作中的角色。研究发现,含有在基序中的变异的(比如:LxxAA;A=丙氨酸)全长SgI不能显著的增加细

之前,有研究人员阐释了一种精浆蛋白-精液凝固蛋白I(SgI)能够作为一种雄激素受体(AR)共激活剂起作用。同时,在AR共调节因子中的一些短序列基序,比如LxxLL(L=亮氨酸),展现出了与AR特异性的互作关系。

最近,有研究人员在体外试验前列腺癌系列中,调查了SgI中LxxLL基序在于AR和细胞生长互作中的角色。研究发现,含有在基序中的变异的(比如:LxxAA;A=丙氨酸)全长SgI不能显著的增加细胞增殖/迁移,以及不能对雄激素调控的AR转录其作用。共沉淀实验比哦啊名,AR与突变的SgI没有物理上的相互作用。另外,SgI的一个18氨基酸多肽且包含LxxLL的转化,而不是LxxAA的转化,能够导致细胞生长和在LNCaP和C4-2系列中前列腺特异性抗原表达的明显的减少。最后,研究人员指出,SgI的LxxLL基序能够成为雄激素敏感和去势难治性前列腺癌的一个新的治疗靶标。

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    2017-12-04 hb2008ye
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    2017-12-04 ylz8405
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    2017-12-03 惠映实验室

    学习了.谢谢.

    0

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    2017-12-02 有备才能无患

    有研究人员阐释了一种精浆蛋白-精液凝固蛋白I(SgI)能够作为一种雄激素受体(AR)共激活剂起作用.同时.在AR共调节因子中的一些短序列基序.比如LxxLL(L=亮氨酸).展现出了与AR特异性的互作关系.

    0

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在前列腺癌发展到去势抵抗性(CRPC)阶段的过程中,雄激素受体(AR)发挥着关键作用。雄激素受体抑制剂不能抑制AR或它的剪接异构体AR-V7的表达,因而没有治疗效果。本研究报道,在AR转录起始位点的上游,酪氨酸激酶ACK1(TNK2)在酪氨酸88上磷酸化组蛋白H4。WDR5/MLL2复合物读取H4-Y88磷酸化标记并沉淀转录性活化H3K4-三甲基标记,从而促进AR转录。以ACK1抑制剂(R)-9b

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背景:雄激素受体(AR)的配体结合域(LBD)的基因突变,如F877l和T878A,已被证实能抑制下一代AR定向疗法。ARN-509-001是一项I/II期研究,该研究主要评估在去势耐受前列腺癌(castration-resistant prostate cancer,CRPC)中apalutamide的活性。apalutamide是一种竞争性雄激素受体抑制剂。本研究中,研究人员评估了apalut

Nat commun:雄激素受体能够增加肾细胞癌的血行转移并减少淋巴转移

透明细胞肾细胞癌(ccRCC)是一种有性别偏向的肿瘤。最近,有研究人员报道了在肺转移和淋巴结转移中同样存在性别差异,表明了阳性雄激素受体(AR)ccRCC也许更倾向于转移到肺而不是淋巴结。研究人员在研究中发现了更高水平的AR表达增加了ccRCC的肺转移并且减少了ccRCC的淋巴结转移。对其的机制解析表明了AR可以通过结合到位于miR-185-5p启动子的雄激素响应元件上来增加miR-185-5p的

JAMA Oncology:PET/CT评估的雄激素受体表达和糖酵解活动作为转移性去势抵抗前列腺癌预后分子标志

雄激素受体信号抑制剂可以延长 转移性去势抵抗前列腺癌患者的生存时间,但是最终肿瘤仍会耐药并继续进展。使用18F-FDG或18F-FDHT PET/CT评估雄激素受体表达可以判断影像学亚型的异质性,这一方法有助于鉴别可以从雄激素受体信号抑制剂获得临床获益的患者。JAMA Oncology近期发表了一篇文章,研究PET/CT评估雄激素受体表达及糖酵解活动是否可以反映肿瘤异质性

Oncogene:雄激素受体调控的脂质合成再激活可促使去势难治性前列腺癌的恶化

雄激素受体(AR)是一种转录激活因子,并且在前列腺癌细胞中可以刺激基因的表达来满足各种细胞功能的需求,包括了代谢和增殖过程。AR信号通路同样对激素依赖的前列腺癌(PCa)的发展是必需的,并且它的活性可以由雄激素阻断疗法(ADTs)来封闭。尽管PCa病人在治疗刚开始对ADTs具有很好的治疗反应,但是癌症不可避免地复发并且恶化到致死性去势难治性前列腺癌(CRPC)。虽然雄激素水平被抑制,AR在CRPC