Butyrate response factor 1 enhances cisplatin sensitivity in human head and neck squamous cell carcinoma cell lines.
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.
Lee
Seung Koo
SK
Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan, Ulsan, Korea.
Kim
Seong Bum
SB
Kim
Jong Soo
JS
Moon
Chang Hoon
CH
Han
Myung Shin
MS
Lee
Byung Ju
BJ
Chung
Dae Kyun
DK
Min
Young Joo
YJ
Park
Jae Hoo
JH
Choi
Dae Hwa
DH
Cho
Hong Rae
HR
Park
Sang Kyu
SK
Park
Jeong Woo
JW
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
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