Bcl-xL/Bax ratio is altered by IFNgamma in TNFalpha- but not in TRAIL-induced apoptosis in colon cancer cell line.
Biochim Biophys Acta
; 1745(1): 101-10, 2005 Aug 15.
Article
en En
| MEDLINE
| ID: mdl-16085058
ABSTRACT
Apoptosis is a crucial mechanism to eliminate harmful cells in which growth factors and cytokines are key regulators. In HT29-D4 cells, a model of human colon carcinoma, IFNgamma presensitization is essential to induce an apoptotic response to TNFalpha whereas it only slightly enhances TRAIL-induced apoptosis. To compare the transcriptional profiles induced by TNFalpha and TRAIL and their regulation by IFNgamma, we optimized a cDNA array analysis on targeted signaling pathways and confirmed the gene expression modulations by comparative RT-PCR. Although the two TNFSF ligands induced a same strong up-expression of pro-apoptotic Bax gene, the expression of anti-apoptotic Bcl-xL gene was more strongly up-regulated in TNFalpha- than in TRAIL-stimulated cells. Thus, TRAIL but not TNFalpha induced apoptotic mitochondrial cascade as highlighted by cytochrome c release into cytosol. IFNgamma presensitization of TRAIL-stimulated cells did not induce any change in cytochrome c release, suggesting that the increase of IFNgamma/TRAIL-induced apoptosis is independent of this pathway. In contrast, IFNgamma pretreatment prevented Bcl-xL gene up-expression in TNFalpha-stimulated cells and allowed cytochrome c release. Thus, we hypothesize that the Bcl-xL/Bax ratio can block the apoptotic response in TNFalpha-stimulated cells but allows cell death initiation when it is altered by a crosstalk between IFNgamma presensitization and TNFalpha induced signalings.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Glicoproteínas de Membrana
/
Interferón gamma
/
Factor de Necrosis Tumoral alfa
/
Apoptosis
/
Proteínas Proto-Oncogénicas c-bcl-2
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2005
Tipo del documento:
Article
País de afiliación:
Francia