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

✍ Scribed by Seung Koo Lee; Seong Bum Kim; Jong Soo Kim; Chang Hoon Moon; Myung Shin Han; Byung Ju Lee; Dae Kyun Chung; Young Joo Min; Jae Hoo Park; Dae Hwa Choi; Hong Rae Cho; Sang Kyu Park; Jeong Woo Park

Publisher: John Wiley and Sons
Year: 2005
Tongue: French
Weight: 456 KB
Volume: 117
Category: Article
ISSN: 0020-7136
DOI: 10.1002/ijc.21133

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✦ Synopsis

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.

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