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IGF-I mediated survival pathways in normal and malignant cells

机译:IGF-I介导的正常和恶性细胞存活途径

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The type-I and -II insulin-like growth factors (IGF-I, II) are now established as survival- or proliferation-factors in many in vitro systems. Of note IGFs provide trophic support for multiple cell types or organ cultures explanted from various species, and delay the onset of programmed cell death (apoptosis) through the mitochondrial (intrinsic pathway) or by antagonizing activation of cytotoxic cytokine signaling (extrinsic pathway). In some instances, IGFs protect against other forms of death such as necrosis or autophagy. The effect of IGFs on cell survival appears to be context specific, being determined both by the cell origin (tissue specific) and the cellular stress that induces loss of cellular viability. In many human cancers, there is a strong association with dysregulated IGF signaling, and this association has been extensively reviewed recently. IGF-regulation is also disrupted in childhood cancers as a consequence of chromosomal translocations. IGFs are implicated also in acute renal failure, traumatic injury to brain tissue, and cardiac disease. This article focuses on the role of IGFs and their cellular signaling pathways that provide survival signals in stressed cells. (c) 2006 Elsevier B.V. All rights reserved.
机译:现在,在许多体外系统中,I型和II型胰岛素样生长因子(IGF-I,II)被确定为生存因子或增殖因子。值得注意的是,IGF为多种细胞类型或从各种物种移植的器官培养提供营养支持,并通过线粒体(内在途径)或拮抗细胞毒性细胞因子信号传导(外在途径)来延迟程序性细胞死亡(细胞凋亡)的发作。在某些情况下,IGF可防止其他形式的死亡,例如坏死或自噬。 IGF对细胞存活的影响似乎是背景特异性的,由细胞起源(组织特异性)和诱导细胞活力丧失的细胞应激共同决定。在许多人类癌症中,IGF信号转导异常密切相关,并且这种相关性最近得到了广泛的审查。由于染色体易位,IGF调节在儿童癌症中也受到破坏。 IGF也与急性肾功能衰竭,脑组织外伤和心脏病有关。本文重点介绍IGF及其在压力细胞中提供生存信号的细胞信号通路的作用。 (c)2006 Elsevier B.V.保留所有权利。

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