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Androgens modulate expression of transcription intermediary factor 2, an androgen receptor coactivator whose expression level correlates with early biochemical recurrence in prostate cancer.
雄激素调节转录中介因子 2 的表达,这是一种雄激素受体共激活剂,其表达水平与前列腺癌的早期生化复发相关。

摘要

Prostate cancer is an androgen-dependent disease; metastatic prostate cancer is typically treated by androgen receptor (AR) blockade. Recurrence after androgen ablation and evidence that AR continues to play a role in many prostate cancers has led to an examination of other factors that potentiate AR activity. AR is a ligand-activated transcription factor whose activity is regulated not only by hormone but also by the levels of coactivators recruited by AR to facilitate transcription. We sought to assess the consequences of reducing expression of the transcription intermediary factor 2 (TIF2) coactivator on prostate cancer cell growth and AR action in cell lines to examine TIF2 expression in prostate cancer and to correlate expression with clinical outcome. Depletion of TIF2 reduced expression of AR-induced target genes and slowed proliferation of AR-dependent and AR-independent prostate cancer cells. Remarkably, we found that TIF2 expression is directly repressed by high levels of androgens in multiple AR-expressing cell lines. Expression of a reporter containing 5'-flanking region of the TIF2 was repressed both by androgens and by the antagonist, Casodex. Expression of TIF2 correlates with biochemical (prostate-specific antigen) recurrence (P = 0.0136). In agreement with our in vitro findings, the highest expression of TIF2 was found in patients whose cancer relapsed after androgen ablation therapy, supporting the idea that AR blockade might activate pathways that lead to stimulation of AR-dependent and AR-independent proliferation of prostate epithelium. The elevated expression of TIF2 at low hormone levels likely aids in inducing AR activity under these conditions; treatment with Casodex has the potential to counteract this induction.

译文

前列腺癌是一种雄激素依赖性疾病; 转移性前列腺癌通常通过雄激素受体 (AR) 阻断来治疗。雄激素消融后的复发和 AR 在许多前列腺癌中继续发挥作用的证据导致了对增强 AR 活性的其他因素的检查。AR 是一种配体激活的转录因子,其活性不仅受激素调节,还受 AR 为促进转录而招募的辅激活剂水平调节。我们试图评估转录中介因子 2 (TIF2) 表达减少的后果共激活因子对前列腺癌细胞生长和 AR 在细胞系中的作用,以检测 TIF2 在前列腺癌中的表达,并将表达与临床结果联系起来。TIF2 的耗竭减少了 AR 诱导的靶基因的表达,并减缓了 AR 依赖性和 AR 非依赖性前列腺癌细胞的增殖。值得注意的是,我们发现在多个 AR 表达的细胞系中,TIF2 的表达被高水平的雄激素直接抑制。含有 TIF2 5 '侧翼区域的报告基因的表达被雄激素和拮抗剂 Casodex 抑制。TIF2 的表达与生化 (前列腺特异性抗原) 复发相关 (P = 0.0136)。与我们的体外研究结果一致,在雄激素消融治疗后癌症复发的患者中发现了 TIF2 的最高表达, 支持 AR 阻断可能激活刺激 AR 依赖性和 AR 非依赖性前列腺上皮增殖的途径的观点。在这些条件下,低激素水平下 TIF2 的表达升高可能有助于诱导 AR 活性; 用 Casodex 治疗有可能抵消这种诱导。

transcription intermediary factor 2

肿瘤 激活蛋白 临床研究术语
概述  :  

转录中介因子2简写为TIF2,也称糖皮质激素受体相互作用蛋白质GRIP1,作为类固醇受体辅激活蛋白(SRC)/p160家族成员之一,通过与其他的核受体超家族成员相互作用发挥其功能。类固醇受体辅激活蛋白家族是第一个被克隆并有最好的特征的一类激活蛋白。它们包括三个同源大类,即SRC-1/NcoA1、TIF2/GRIP1/SRC-2/NcoA2和pCIP/ACTR/AIB1/RAC3/TRAM1/SRC-3/NcoA3。TIF2/GRIP1/SRC-2/NcoA2是一类相对分子质量约为160 kD

Transcription   英 /træn'skrɪpʃ(ə)n; trɑːn-/   美 /træn'skrɪpʃən/

释    义   n. 抄写;抄本;誊写

例    句   Gene expression in eukaryotes is regulated primarily at the level of transcription. 真核生物中基因表达的调节主要受转录水平的调控。

 

Intermediary   英 /,ɪntə'miːdɪərɪ/   美 /,ɪntɚ'midɪɛri/

释    义   adj. 中间的;媒介的;中途的;n. 中间人;仲裁者;调解者;媒介物;复数 intermediaries

同根词   intermediate adj. 中间的,中级的;interlocutory adj. 中间的;对话的;对话体的;intermediately adv. 在中间;intermediate n. [化学] 中间物;媒介;

例    句   Schema as an intermediary to communicate the intellectual and sensibility, through which our knowledge becomes possible. 图型作为一种中介,沟通着知性与感性,从而使我们的知识成为可能。

 

Factor   英 /'fæktə/   美 /'fæktɚ/

释    义   n. 因素;要素;[物] 因数;代理人;vi. 做代理商;vt. 把…作为因素计入;代理经营;把…分解成

同根词   factory n. 工厂;制造厂;代理店;factoring n. [数] 因子分解,[数] 因式分解;保付代理;factorization n. [数] 因子分解;[数] 因式分解;

例    句   So, it should consider the relationship of each corrosion factor on evaluation of corrosion effect. 因此,在评价腐蚀效应时应综合考虑各腐蚀因子之间的相关关系。

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