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Transcription factor Sp1, also known as specificity protein 1 as a therapeutic target

机译:转录因子Sp1,也称为特异性蛋白1作为治疗靶标

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Introduction: Specificity protein (Sp) transcription factors (TFs) are members of the Sp/Kruppel-like factor family, and Sp proteins play an important role in embryonic and early postnatal development. Sp1 has been the most extensively investigated member of this family, and expression of this protein decreases with age, whereas Sp1 and other family members (Sp3 and Sp4) are highly expressed in tumors and cancer cell lines.Area covered: The prognostic significance of Sp1 in cancer patients and the functional pro-oncogenic activities of Sp1, Sp3 and Sp4 in cancer cell lines are summarized. Several different approaches have been used to target downregulation of Sp TFs and Sp-regulated genes, and this includes identification of different structural classes of antineoplastic agents including NSAIDs, natural products and their synthetic analogs and several well-characterized drugs including arsenic trioxide, aspirin and metformin. The multiple pathways involved in drug-induced Sp downregulation are also discussed.Expert opinion: The recognition by the scientific and clinical community that experimental and clinically used antineoplastic agents downregulate Sp1, Sp3 and Sp4, and pro-oncogenic Sp-regulated genes will facilitate future clinical applications for individual drug and drug combination therapies that take advantage of their unusual effects.
机译:简介:特异性蛋白(Sp)转录因子(TFs)是Sp / Kruppel样因子家族的成员,并且Sp蛋白在胚胎和出生后早期发育中起重要作用。 Sp1是该家族中研究最广泛的成员,该蛋白的表达随年龄而降低,而Sp1和其他家族成员(Sp3和Sp4)在肿瘤和癌细胞系中高度表达。总结了癌症患者中Sp1,Sp3和Sp4的功能促癌活性。已经使用了几种不同的方法来靶向Sp TF和Sp调控基因的下调,这包括鉴定不同结构类别的抗肿瘤药,包括NSAID,天然产物及其合成类似物,以及几种具有很好特征的药物,包括三氧化二砷,阿司匹林和二甲双胍。还讨论了药物诱导的Sp下调的多种途径。专家意见:科学和临床界认识到实验和临床使用的抗肿瘤药物下调Sp1,Sp3和Sp4以及促癌的Sp调控基因将为未来的发展提供便利利用其非凡效果的个体药物和药物联合疗法的临床应用。

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