دورية أكاديمية
أعرض في EDS

Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death: Relationship to Bcl-2 family and caspase activation.

التفاصيل البيبلوغرافية
العنوان: Imatinib enhances human melanoma cell susceptibility to TRAIL-induced cell death: Relationship to Bcl-2 family and caspase activation.
المؤلفون: Hamaï A; INSERM, U753, Laboratoire d'Immunologie des Tumeurs Humaines: Interaction effecteurs cytotoxiques-système tumoral, Institut Gustave Roussy PR1 and IFR 54, Villejuif, France., Richon C, Meslin F, Faure F, Kauffmann A, Lecluse Y, Jalil A, Larue L, Avril MF, Chouaib S, Mehrpour M
المصدر: Oncogene [Oncogene] 2006 Dec 07; Vol. 25 (58), pp. 7618-34. Date of Electronic Publication: 2006 Sep 18.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0950-9232 (Print) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE
أسماء مطبوعة: Publication: <2002->: Basingstoke : Nature Publishing Group
Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-
مواضيع طبية MeSH: Antineoplastic Agents/*pharmacology , Apoptosis/*drug effects , Caspases/*metabolism , Melanoma/*pathology , Piperazines/*pharmacology , Proto-Oncogene Proteins c-bcl-2/*metabolism , Pyrimidines/*pharmacology , TNF-Related Apoptosis-Inducing Ligand/*pharmacology, Benzamides ; Cell Culture Techniques ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Enzyme Activation ; Gene Expression Profiling ; Humans ; Imatinib Mesylate ; Melanoma/genetics ; Melanoma/metabolism ; Neoplasm Metastasis/genetics ; Neoplasm Metastasis/pathology ; Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Proteins c-kit/metabolism ; Receptors, TNF-Related Apoptosis-Inducing Ligand/metabolism ; Recombinant Proteins/pharmacology
مستخلص: In order to define genetic determinants of primary and metastatic melanoma cell susceptibility to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), we have applied oligonucleotide microarrays to TRAIL-sensitive primary T1 cells and TRAIL-resistant metastatic G1 cells treated or not with TRAIL. T1 and G1 cells are isogenic melanoma cell subclones. We examined 22 000 spots, 4.2% of which displayed differential expression in G1 and T1 cells. Cell susceptibility to TRAIL-mediated apoptosis was found to be correlated with gene expression signatures in this model. Some of the differentially expressed genes were identified as involved in ATP-binding and signaling pathways, based on previously published data. Further analysis provided evidences that c-kit was overexpressed in G1 cells while it was absent in T1 cells. The c-kit inhibitor, imatinib, did not restore TRAIL sensitivity, excluding a role for c-kit in TRAIL resistance in G1 cells. Surprisingly, imatinib inhibited cell proliferation and TRAIL-mediated apoptosis in melanoma cells. We investigated the possible involvement of several molecules, including c-ABL, platelet-derived growth factor receptor (PDGFR), cellular FADD-like interleukin-1 alpha-converting enzyme-like inhibitory protein (c-FLIP)(L/S), Fas-associated DD kinase, p53, p21(WAF1), proteins of B-cell leukemia/lymphoma 2 (Bcl-2) family and cytochrome c. Imatinib did not modulate the expression or activation of its own targets, such as c-ABL, PDGFRalpha and PDGFRbeta, but it did affect the expression of c-FLIP(L), BCL2-associated X protein (Bax) and Bcl-2. Moreover, c-FLIP(L) knockdown sensitized T1 cells to TRAIL-mediated apoptosis, with a sensitivity similar to that of cells previously treated with imatinib. More notably, we found that the resistance to TRAIL in G1 cells was correlated with constitutive c-FLIP(L) recruitment to the DISC and the inhibition of caspase 8, 3 and 9 processing. Moreover, c-FLIP(L) knockdown partly restored TRAIL sensitivity in G1 cells, indicating that the expression level of c-FLIP(L) and its interaction with TRAIL receptor2 play a crucial role in determining TRAIL resistance in metastatic melanoma cells. Our results also show that imatinib enhances TRAIL-induced cell death independently of BH3-interacting domain death agonist translocation, in a process involving the Bax:Bcl-X(L) ratio, Bax:Bcl-X(L)/Bcl-2 translocation, cytochrome c release and caspase activation. Our data indicate that imatinib sensitizes T1 cells by directly downregulating c-FLIP(L), with the use of an alternative pathway for antitumor activity, because PDGFRalpha is not activated in T1 cells and these cells do not express c-kit, c-ABL or PDGFRbeta. Caspase cascade activation and mitochondria also play a key role in the imatinib-mediated sensitization of melanoma cells to the proapoptotic action of TRAIL.
التعليقات: Erratum in: Oncogene. 2007 Feb 22;26(8):1256.
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Benzamides)
0 (Piperazines)
0 (Proto-Oncogene Proteins c-bcl-2)
0 (Pyrimidines)
0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
0 (Recombinant Proteins)
0 (TNF-Related Apoptosis-Inducing Ligand)
0 (TNFSF10 protein, human)
8A1O1M485B (Imatinib Mesylate)
EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
EC 3.4.22.- (Caspases)
تواريخ الأحداث: Date Created: 20060920 Date Completed: 20070116 Latest Revision: 20151119
رمز التحديث: 20240628
DOI: 10.1038/sj.onc.1209738
PMID: 16983347
قاعدة البيانات: MEDLINE
الوصف
تدمد:0950-9232
DOI:10.1038/sj.onc.1209738