IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model
IGF-1R and ErbB3/HER3 contribute to enhanced proliferation and carcinogenesis in trastuzumab-resistant ovarian cancer model
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DOI：
10.1016/j.bbrc.2013.06.030
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发表时间：
2013-07-12
影响因子：
3.1
通讯作者：
Peng, Hui
中科院分区：
文献类型：
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作者：
Jia, Yanhan;Zhang, Yan;Peng, Hui
曲妥珠单抗（赫赛汀）已在几种类型的HER 2过表达人类癌症中显示出临床潜力。然而，原发性和获得性耐药发生在许多HER 2阳性患者的方案。为了研究对曲妥珠单抗获得性治疗耐药的可能机制，我们建立了一种具有较强致癌性的人卵巢癌细胞SKOV 3/T的临床前模型。通过基因芯片分析探索亲本和耐药细胞之间的基因表达差异，其中IGF-1 R和HER 3被检测到是起作用的关键分子。通过RT-PCR、shRNA介导的基因敲减、下游信号激活、细胞周期分布和存活等后续实验验证了其正确性。这些结果表明，IGF-1 R和HER 3差异调节曲妥珠单抗耐药性，可能是卵巢癌曲妥珠单抗治疗的有前途的目标。(C)2013 Elsevier Inc. All rights reserved.
Trastuzumab (Herceptin) has demonstrated clinical potential in several types of HER2-overexpressing human cancers. However, primary and acquired resistance occurs in many HER2-positive patients with regimens. To investigate the possible mechanism of acquired therapeutic resistance to trastuzumab, we have developed a preclinical model of human ovarian cancer cells, SKOV3/T, with the distinctive feature of stronger carcinogenesis. The differences in gene expression between parental and the resistant cells were explored by microarray analysis, of which IGF-1R and HER3 were detected to be key molecules in action. Their correctness was validated by follow-up experiments of RT-PCR, shRNA-mediated knockdown, downstream signal activation, cell cycle distribution and survival. These results suggest that IGF-1R and HER3 differentially regulate trastuzumab resistance and could be promising targets for trastuzumab therapy in ovarian cancer. (C) 2013 Elsevier Inc. All rights reserved.