Bcl-xL/Bax ratio is altered by IFNgamma in TNFalpha- but not in TRAIL-induced apoptosis in colon cancer cell line
| Autor: | F Garrouste, Gilbert Pommier, Gilbert Baillat, M Remacle-Bonnet, Jacques Marvaldi |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Programmed cell death
bcl-X Protein Bcl-xL Apoptosis TNF-Related Apoptosis-Inducing Ligand Interferon-gamma Bcl-2 family Cell Line Tumor Gene expression Humans Molecular Biology bcl-2-Associated X Protein Membrane Glycoproteins biology Tumor Necrosis Factor-alpha Cytochrome c Cytochromes c Cell Biology Colon cancer Cell biology Tumor necrosis factor superfamily Proto-Oncogene Proteins c-bcl-2 Colonic Neoplasms biology.protein Tumor necrosis factor alpha Signal transduction Apoptosis Regulatory Proteins cDNA array IFNγ |
| Zdroj: | Biochimica et biophysica acta. 1745(1) |
| ISSN: | 0006-3002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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