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对用野生型p53和细胞毒性化疗处理的胶质母细胞瘤细胞系进行蛋白质组学研究,结果表明半乳糖凝集素-1与p53表达之间存在关联。

Proteomic investigation of glioblastoma cell lines treated with wild-type p53 and cytotoxic chemotherapy demonstrates an association between galectin-1 and p53 expression.

作者信息

Puchades Maja, Nilsson Carol L, Emmett Mark R, Aldape Kenneth D, Ji Yongjie, Lang Frederick F, Liu Ta-Jen, Conrad Charles A

机构信息

Institute of Neuroscience and Physiology, Sahlgrenska Academy, Göteborg University, SU/Mölndal, SE-43180 Mölndal, Sweden.

出版信息

J Proteome Res. 2007 Feb;6(2):869-75. doi: 10.1021/pr060302l.

Abstract

Global protein analysis of treated and untreated glioblastoma cell lines was performed. Proteomic analysis revealed the identity of proteins that were significantly modulated by the treatment with wild-type TP53 and the cytotoxic chemotherapy SN38. In particular, galectin-1 was found to be negatively regulated by transfection with TP53 and further down-regulated by SN38. Expression level changes were confirmed by Western blot. Subsequent analysis of several high-grade glioma cell lines demonstrated very high levels of galectin-1, regardless if the cell lines contained mutant or wild-type TP53. High expression of galectin-1 in a human orthotopic murine tumor model was also detected by immunohistochemistry and revealed a consistent pattern of preferential expression in peripheral or leading tumor edges. Further examination of galectin-1 expression through microarray analysis in tumor materials from patients confirmed galectin-1 as a valuable biomarker and possible therapeutic target. These results demonstrate the utility of using proteomic approaches to interrogate and identify potential useful targets for cancer therapy by evaluating specific tumor responses, either positive or negative, to various therapies.

摘要

对经过处理和未处理的胶质母细胞瘤细胞系进行了全球蛋白质分析。蛋白质组学分析揭示了经野生型TP53和细胞毒性化疗药物SN38处理后显著调节的蛋白质的身份。特别是,发现半乳糖凝集素-1通过转染TP53被负调控,并被SN38进一步下调。通过蛋白质印迹法证实了表达水平的变化。随后对几种高级别胶质瘤细胞系的分析表明,无论细胞系含有突变型还是野生型TP53,半乳糖凝集素-1的水平都非常高。通过免疫组织化学在人原位小鼠肿瘤模型中也检测到半乳糖凝集素-1的高表达,并揭示了在外周或肿瘤前缘优先表达的一致模式。通过对患者肿瘤材料进行微阵列分析进一步检查半乳糖凝集素-1的表达,证实半乳糖凝集素-1是一种有价值的生物标志物和可能的治疗靶点。这些结果证明了使用蛋白质组学方法通过评估各种疗法的特异性肿瘤反应(无论是阳性还是阴性)来探究和识别癌症治疗潜在有用靶点的实用性。

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