title: Butyrate response factor 1 enhances cisplatin sensitivity in human head and neck squamous cell carcinoma cell lines.
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.
authors.affiliation: Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan, Ulsan, Korea.
authors.forename: Seung Koo
authors.initials: SK
authors.lastname: Lee
authors.forename: Seong Bum
authors.initials: SB
authors.lastname: Kim
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Chang Hoon
authors.initials: CH
authors.lastname: Moon
authors.forename: Myung Shin
authors.initials: MS
authors.lastname: Han
authors.forename: Byung Ju
authors.initials: BJ
authors.lastname: Lee
authors.forename: Dae Kyun
authors.initials: DK
authors.lastname: Chung
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Min
authors.forename: Jae Hoo
authors.initials: JH
authors.lastname: Park
authors.forename: Dae Hwa
authors.initials: DH
authors.lastname: Choi
authors.forename: Hong Rae
authors.initials: HR
authors.lastname: Cho
authors.forename: Sang Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Jeong Woo
authors.initials: JW
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism; D051817:Butyrate Response Factor 1; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D051817:Butyrate Response Factor 1; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D011506:Proteins; C102034:ZFP36L1 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin