Phosphorylated ribosomal S6 (p-rpS6) as a post-treatment indicator of HER2 signalling targeted drug resistance

被引：11

作者：

Yang-Kolodji, Gloria ^{[1
]}

Mumenthaler, Shannon M. ^{[2
]}

Mehta, Arjun ^{[1
]}

Ji, Lingyun ^{[3
]}

Tripathy, Debu ^{[1
,4
]}

机构：

[1] Univ So Calif, Dept Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA

[2] Univ So Calif, Ctr Appl Mol Med, Los Angeles, CA 90033 USA

[3] Univ So Calif, Dept Prevent Med, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA

[4] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX USA

来源：

BIOMARKERS | 2015年 / 20卷 / 05期

关键词：

Biomarker; breast cancer; cell model; drug response; trastuzumab resistance; METASTATIC BREAST-CANCER; OVERCOMING RESISTANCE; PARADIGM-SHIFT; SINGLE-AGENT; TRASTUZUMAB; LAPATINIB; SURVIVAL; EFFICACY; SAFETY; KI67;

D O I：

10.3109/1354750X.2015.1068865

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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.

引用

页码：313 / 322

页数：10

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