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

Autor: David F. Stroncek, Hang Gao, Ping Jin, Qinghua Zeng, Shirong Li, Xue-Jin Su, Suchan Liao, Yu-Lin Li, Zhi-Xiang Xu, Ying-Xian Zhai, Bo Ren, Shutong Liu
Rok vydání: 2017
Předmět:
0301 basic medicine
Oncology
medicine.medical_specialty
Cell Survival
Cell
lcsh:Medicine
BAG-1
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
Internal medicine
Gene expression
medicine
Humans
Cisplatin
Squamous Cell Carcinoma of Head and Neck
business.industry
Research
lcsh:R
Head and neck squamous cell carcinomas
Reproducibility of Results
Biomarker
General Medicine
medicine.disease
Head and neck squamous-cell carcinoma
Up-Regulation
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
stomatognathic diseases
030104 developmental biology
medicine.anatomical_structure
Drug Resistance
Neoplasm
Head and Neck Neoplasms
Tumor progression
Cell culture
Drug resistance
BCL-xL
030220 oncology & carcinogenesis
Carcinoma
Squamous Cell
Biomarker (medicine)
DNA microarray
business
Signal Transduction
Transcription Factors
medicine.drug
Zdroj: Journal of Translational Medicine
Journal of Translational Medicine, Vol 15, Iss 1, Pp 1-11 (2017)
ISSN: 1479-5876
DOI: 10.1186/s12967-017-1289-2
Popis: Background In 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. Methods Primary 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. Results Advanced 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. Conclusion Increased 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. Electronic supplementary material The online version of this article (doi:10.1186/s12967-017-1289-2) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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