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[信号转导和转录激活因子蛋白在恶性肿瘤发生及治疗中的作用]

[STAT proteins in cancerogenesis and therapy of malignancies].

作者信息

Konjević Gordana

出版信息

Srp Arh Celok Lek. 2009 Jan-Feb;137(1-2):98-105. doi: 10.2298/sarh0902098k.

DOI:10.2298/sarh0902098k
PMID:19370975
Abstract

Signal transducers and activators of transcription (STAT) proteins are a 7-member family of cytoplasmic transcription factors that participate in signal transduction by cytokines, hormones, and growth factors. STAT proteins control the most important cellular processes, including survival, proliferation and differentiation. A great number of cytokines and other factors in different cell types activate STAT1, STAT3 and STAT5 and in this manner regulate processes such as cellular proliferation, differentiation and survival. STATs such as STAT4 and STAT6 have a more specific effect and are engaged in the differentiation of T helper cell populations. Given the critical roles of STAT proteins it has been established in many studies that STAT3 and STAT5 are oncogenes that can contribute to cellular transformation by increasing proliferation and slowing-down apoptosis. On the other hand, STAT1 is a tumour suppressor gene and its inactivation contributes to malignant transformation. Initially STAT proteins were extensively studied in leukaemias, but later their role in the development of different solid tumours has been also shown. Aside from their role in the development of tumours, STAT1, STAT3 and STAT5 can be considered as molecular markers for early detection of certain types of tumours, as well as prognostic factors in the determination of tumour aggressiveness and predictors of response to various types of therapy. Evidence of the deregulation of STAT signalling pathway can serve as a basis for designing novel targeted molecular therapeutic strategies that carry a great potential in the therapy of solid tumours and leukaemias.

摘要

信号转导子和转录激活子(STAT)蛋白是一个由7个成员组成的细胞质转录因子家族,它们通过细胞因子、激素和生长因子参与信号转导。STAT蛋白控制着最重要的细胞过程,包括存活、增殖和分化。不同细胞类型中的大量细胞因子和其他因子激活STAT1、STAT3和STAT5,并以此方式调节细胞增殖、分化和存活等过程。诸如STAT4和STAT6等STAT蛋白具有更特定的作用,参与辅助性T细胞群体的分化。鉴于STAT蛋白的关键作用,许多研究已证实,STAT3和STAT5是癌基因,可通过增加增殖和减缓细胞凋亡促进细胞转化。另一方面,STAT1是一种肿瘤抑制基因,其失活会导致恶性转化。最初,STAT蛋白在白血病中得到广泛研究,但后来也显示了它们在不同实体瘤发生中的作用。除了在肿瘤发生中的作用外,STAT1、STAT3和STAT5还可被视为某些类型肿瘤早期检测的分子标志物,以及确定肿瘤侵袭性的预后因素和对各种治疗反应的预测指标。STAT信号通路失调的证据可作为设计新型靶向分子治疗策略的基础,这些策略在实体瘤和白血病治疗中具有巨大潜力。

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STAT3 genetic variant, alone and in combination with STAT5b polymorphism, contributes to breast cancer risk and clinical outcomes.信号转导和转录激活因子3(STAT3)基因变异,单独或与信号转导和转录激活因子5b(STAT5b)基因多态性共同作用,会影响乳腺癌风险及临床预后。
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