GIPC mediates the generation of reactive oxygen species and the regulation of cancer cell proliferation by insulin-like growth factor-1/IGF-1R signaling
GIPC mediates the generation of reactive oxygen species and the regulation of cancer cell proliferation by insulin-like growth factor-1/IGF-1R signaling
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DOI：
10.1016/j.canlet.2010.02.007
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发表时间：
2010-08-28
期刊：
影响因子：
9.7
通讯作者：
You, Hye Jin
中科院分区：
文献类型：
--
作者：
Choi, Ji Seung;Paek, A. Rome;You, Hye Jin
胰岛素样生长因子-1（IGF-1）/IGF-1受体信号传导参与多种细胞过程，包括细胞存活、生长和增殖。IGF-1 R的表达增加及其下游信号成分的激活与人类癌症有关。虽然IGF-1 R的调节作用已经确立，但IGF-1 R与其结合伴侣之间的关系尚不清楚。GAIP相互作用蛋白C末端（GIPC）在促进细胞增殖方面仍不清楚。我们发现siRNA介导的GIPC表达沉默降低了乳腺癌模型中IGF-1介导的IGF-1 R磷酸化和细胞增殖。IGF-1介导的细胞增殖也受到N-乙酰半胱氨酸的抑制，这与活性氧的产生有关。siRNA介导的GIPC表达沉默也降低了IGF-1介导的活性氧的产生。总之，这些数据表明，GIPC有助于IGF-1诱导的癌细胞增殖通过调节活性氧的产生。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Insulin-like growth factor-1 (IGF-1)/IGF-1 receptor signaling participates in a variety of cellular processes, including cell survival, growth, and proliferation. Increased expression of IGF-1R and activation of its downstream signaling components have been implicated in human cancers. Although a regulatory role for IGF-1R has been established, the relationship between IGF-1R and its binding partner. GAIP-interacting protein C-terminus (GIPC), in terms of promoting cell proliferation, remains unclear. We found that siRNA-mediated silencing of GIPC expression decreased IGF-1-mediated IGF-1R phosphorylation and cellular proliferation in breast cancer models. IGF-1-mediated cellular proliferation was also inhibited by N-acetylcysteine, which implicates reactive oxygen species generation. siRNA-mediated silencing of GIPC expression also decreased IGF-1-mediated reactive oxygen species generation. Taken together, these data suggest that GIPC contributes to IGF-1-induced cancer cell proliferation via the regulation of reactive oxygen species production. (C) 2010 Elsevier Ireland Ltd. All rights reserved.