Abstract:
:Caspase-8 is a critical upstream mediator of apoptosis in the death receptor pathway. However, the relationship between caspase-8 mutation and chemosensitivity remain unclear in head and neck squamous cell carcinoma (HNSCC) carrying p53 mutation. In this study, we identified a caspase-8 nonsense mutation, accompanied by the loss of the second allele, in a drug-resistant HOC313 HNSCC cell line. The nonsense mutation (R68X) leads to truncation of all defined functional domains. Reconstitution of caspase-8 by stable transfection of wild-type caspase-8 sensitized the cells to cisplatin-, but not etoposide-induced apoptosis. Consistent with this, cisplatin, but not etoposide, induced TNF-alpha and TRAIL mRNA in caspase-8 reconstituted HOC313 cells, accompanied by activation of the reconstituted caspase-8 and its downstream caspase-3. These results indicate that the loss of caspase-8 plays an important role in acquisition of chemoresistance to cisplatin in HOC313 cells.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Liu J,Uematsu H,Tsuchida N,Ikeda MAdoi
10.1016/j.bbrc.2009.10.090subject
Has Abstractpub_date
2009-12-18 00:00:00pages
989-94issue
3eissn
0006-291Xissn
1090-2104pii
S0006-291X(09)02081-6journal_volume
390pub_type
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更新日期:2011-08-26 00:00:00