磷酸化核糖体S6（p-rpS6）作为HER2信号靶向耐药性的治疗后指标。
Phosphorylated ribosomal S6 (p-rpS6) as a post-treatment indicator of HER2 signalling targeted drug resistance.
作者信息
Yang-Kolodji Gloria, Mumenthaler Shannon M, Mehta Arjun, Ji Lingyun, Tripathy Debu
机构信息
a Department of Medicine , Norris Comprehensive Cancer Center, University of Southern California , Los Angeles , CA , USA .
出版信息
Biomarkers. 2015;20(5):313-22. doi: 10.3109/1354750X.2015.1068865.
Abstract
OBJECTIVE
To identify clinically relevant predictive biomarkers of trastuzumab resistance.
MATERIAL AND METHODS
MTT, FACS assays, immunoblotting and immunocytochemistry were used to phenotypically characterize drug responses of two cell models BT474R and SKBR3R. Student's t-test and Spearman's correlation were applied for statistic analysis.
RESULTS
The activity of a downstream effector of the HER2 pathway phosphorylated ribosomal protein S6 (p-rpS6), was suppressed by trastuzumab in the parental cell lines yet remained unchanged in the resistant cells following treatment. The level of p-rpS6 was inversely correlated to the drug induced growth inhibition of trastuzumab-resistant cells when they are treated with selected HER2 targeting drugs.
CONCLUSION
p-rpS6 is a robust post-treatment indicator of HER2 pathway-targeted therapy resistance.
摘要
目的
确定曲妥珠单抗耐药的临床相关预测生物标志物。
材料与方法
采用MTT、流式细胞术检测、免疫印迹和免疫细胞化学方法对两种细胞模型BT474R和SKBR3R的药物反应进行表型特征分析。采用学生t检验和Spearman相关性分析进行统计学分析。
结果
HER2途径的下游效应物磷酸化核糖体蛋白S6（p-rpS6）的活性在亲本细胞系中被曲妥珠单抗抑制，但在耐药细胞系中处理后保持不变。当用选定的HER2靶向药物处理时，p-rpS6的水平与曲妥珠单抗耐药细胞的药物诱导生长抑制呈负相关。
结论
p-rpS6是HER2途径靶向治疗耐药的有力治疗后指标。
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