Over-expression of BAG-1 in head and neck squamous cell carcinomas (HNSCC) is associated with cisplatin-resistance

Journal of Translational Medicine

Research

Ping Jin¹  David Stroncek¹  Xue-Jin Su²  Bo Ren²  Shirong Li²  Hang Gao²  Yulin Li²  Ying-Xian Zhai²  Shutong Liu³  Suchan Liao⁴  Zhixiang Xu⁵  Qinghua Zeng⁵ 

[1] Cell Processing Section, Department of Transfusion, Clinical Center, National Institutes of Health, 20892, Bethesda, MD, USA;The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, Changchun, Jilin, China;The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, Changchun, Jilin, China;Cell Processing Section, Department of Transfusion, Clinical Center, National Institutes of Health, 20892, Bethesda, MD, USA;The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, Changchun, Jilin, China;Department of Physiology, Youjiang Medical University for Nationalities, 533000, Baise, Guangxi, China;The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, 130021, Changchun, Jilin, China;Division of Hematology/Oncology, Department of Medicine, University of Alabama at Birmingham, 35294, Birmingham, AL, USA;

关键词: Head and neck squamous cell carcinomas;    Cisplatin;    Drug resistance;    Biomarker;    BAG-1;    BCL-xL;   

DOI  :  10.1186/s12967-017-1289-2

 received in 2017-08-07, accepted in 2017-08-24,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundIn order to improve therapy for head and neck squamous cell carcinoma (HNSCC), biomarkers associated with local and/or distant tumor relapses and cancer drug resistance are urgently needed. This study identified a potential biomarker, Bcl-2 associated athanogene-1 (BAG-1), that is implicated in HNSCC insensitive to cisplatin and tumor progression.MethodsPrimary and advanced (relapsed from parental) University of Michigan squamous cell carcinoma cell lines were tested for sensitivity to cisplatin and gene expression profiles were compared between primary (cisplatin sensitive) and the relapsed (cisplatin resistant) cell lines by using Agilent microarrays. Additionally, differentially expressed genes phosphorylated AKT, and BAG-1, and BCL-xL were evaluated for expression using HNSCC tissue arrays.ResultsAdvanced HNSCC cells revealed resistant to cisplatin accompanied by increased expression of BAG-1 protein. siRNA knockdown of BAG-1 expression resulted in significant improvement of HNSCC sensitivity to cisplatin. BAG-1 expression enhanced stability of BCL-xL and conferred cisplatin resistant to the HNSCC cells. In addition, high levels of expression of phosphorylated AKT, BAG-1, and BCL-xL were observed in advanced HNSCC compared to in that of primary HNSCC.ConclusionIncreased expression of BAG-1 was associated with cisplatin resistance and tumor progression in HNSCC patients and warrants further validation in larger independent studies. Over expression of BAG-1 may be a biomarker for cisplatin resistance in patients with primary or recurrent HNSCCs and targeting BAG-1 could be helpful in overcoming cisplatin resistance.

【 授权许可】

CC BY   
© The Author(s) 2017