Butyrate response factor 1 enhances cisplatin sensitivity in human head and neck squamous cell carcinoma cell lines.

TitleButyrate response factor 1 enhances cisplatin sensitivity in human head and neck squamous cell carcinoma cell lines.
Publication TypeJournal Article
Year of Publication2005
AuthorsLee SKoo, Kim SBum, Kim JSoo, Moon CHoon, Han MShin, Lee BJu, Chung DKyun, Min YJoo, Park JHoo, Choi DHwa, Cho HRae, Park SKyu, Park JWoo
JournalInt J Cancer
Volume117
Issue1
Pagination32-40
Date Published2005 Oct 20
ISSN0020-7136
KeywordsAntineoplastic Agents, Apoptosis, Base Sequence, Biomarkers, Tumor, Butyrate Response Factor 1, Carcinoma, Squamous Cell, Caspase 3, Caspases, Cisplatin, DNA-Binding Proteins, Drug Resistance, Neoplasm, Gene Expression Profiling, Head and Neck Neoplasms, Humans, Immediate-Early Proteins, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Proteins, Tumor Cells, Cultured
Abstract

Cisplatin is a widely used chemotherapeutic agent in head and neck squamous cell carcinoma (HNSCC). Resistance to cisplatin is a common feature of HNSCC. To identify genes that may regulate cisplatin sensitivity, we carried out a cDNA microarray analysis of gene expression in cisplatin-sensitive and cisplatin-resistant HNSCC-derived cell lines. Among genes differentially expressed by cisplatin treatment, we have confirmed the elevated expression of butyrate responsive factor 1 (BRF1) in cisplatin-sensitive HNSCC cells and have demonstrated that the expression level of BRF1 is associated with cisplatin-sensitivity. Specific inhibition of BRF1 expression using an antisense oligodeoxynucleotide (ODN) decreased the cisplatin-sensitivity and, on the contrary, overexpression of BRF1 increased cisplatin-sensitivity in HNSCC cells. Elevated expression of BRF1 decreased the level of the human inhibitor of apoptosis protein-2 (cIAP2) and increased the caspase-3 activity in HNSCC cells. In addition, elevated expression of BRF1 decreased the expression level of enhanced green fluorescent protein (EGFP) linked to a 3' terminal AU-rich element (ARE) of cIAP2 mRNA. These findings demonstrate that BRF1 expression enhanced cisplatin sensitivity in HNSCC cells by reducing the levels of cIAP2 mRNA.

DOI10.1002/ijc.21133
Alternate JournalInt J Cancer
PubMed ID15880358
Related Institute: 
Molecular Imaging Innovations Institute (MI3)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065