IGF-1 受体在辐射反应中的作用。
Role of IGF-1 receptor in radiation response.
机构信息
Instituto Canario de Investigación del Cáncer, Canary Islands, Spain.
出版信息
Transl Oncol. 2012 Feb;5(1):1-9. doi: 10.1593/tlo.11265. Epub 2012 Feb 1.
Abstract
Insulin-like growth factor 1 receptor (IGF-1R) is a transmembrane receptor tyrosine kinase involved in the development and progression of cancer whose activation strongly promotes cell growth and survival. IGF-1R exerts its main actions through the activation of the mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. In addition to their traditional roles, IGF-1R activation has been associated with increased radioresistance both in vitro and in vivo, although the molecular mechanisms behind this process are still unclear. Recently, IGF-1R has been associated to new partners as major vault proteins, BCL-2, BAX, or Ku70/80, related to radiochemotherapy resistance, regulation of apoptosis, and nonhomologous end-joining DNA repair. Here, we review these novel associations of IGF-1R trying to explain the resistance to radiotherapy mediated by IGF-1R. Finally, we revised the role of new therapies leading to block the receptor to enhance the efficacy of radiation.
摘要
胰岛素样生长因子 1 受体（IGF-1R）是一种跨膜受体酪氨酸激酶，参与癌症的发生和发展，其激活强烈促进细胞生长和存活。IGF-1R 通过激活丝裂原活化蛋白激酶和磷酸肌醇 3-激酶途径发挥其主要作用。除了它们的传统作用外，IGF-1R 的激活与体外和体内的放射抗性增加有关，尽管这一过程背后的分子机制尚不清楚。最近，IGF-1R 与主要穹窿蛋白、BCL-2、BAX 或 Ku70/80 等新的伙伴蛋白相关联，这些蛋白与放化疗耐药、细胞凋亡调节和非同源末端连接 DNA 修复有关。在这里，我们综述了 IGF-1R 的这些新的关联，试图解释 IGF-1R 介导的放射治疗抵抗。最后，我们回顾了导致阻断受体以增强辐射疗效的新疗法的作用。
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2
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