Title : GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells.

Pub. Date : 2007 Jan

PMID : 17166886






7 Functional Relationships(s)
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1 GADD153 mediates celecoxib-induced apoptosis in cervical cancer cells. Celecoxib DNA damage inducible transcript 3 Homo sapiens
2 Screening of a microarray cDNA-chip containing 225 different genes revealed that growth arrest and DNA damage inducible gene (GADD153), a transcription factor involved in apoptosis, showed the strongest differential expression following celecoxib treatment in all three cervical cancer cell lines. Celecoxib DNA damage inducible transcript 3 Homo sapiens
3 Notably, siRNA-induced silencing of GADD153 suppressed celecoxib-induced apoptosis in all the three cell lines, and exogenous expression of GADD153 triggered apoptosis in cervical cancer cells in the absence of other apoptotic stimuli. Celecoxib DNA damage inducible transcript 3 Homo sapiens
4 A luciferase reporter gene assay and mRNA stability tests revealed that expression of GADD153 was regulated at both the transcriptional and post-transcriptional levels following celecoxib treatment. Celecoxib DNA damage inducible transcript 3 Homo sapiens
5 The region between -649 and -249, containing an intact C/EBP-ATF binding site, was required for the basal activity and celecoxib-induced stimulation of GADD153 promoter activity. Celecoxib DNA damage inducible transcript 3 Homo sapiens
6 Also, mRNA stability test showed that celecoxib prolonged the half-life of GADD153 mRNA. Celecoxib DNA damage inducible transcript 3 Homo sapiens
7 These novel findings collectively suggest that GADD153 may play a key role in celecoxib-induced apoptosis in cervical cancer cells by regulating the expression of proapoptotic proteins such as Bak. Celecoxib DNA damage inducible transcript 3 Homo sapiens