6533b82efe1ef96bd1293202

RESEARCH PRODUCT

PED is overexpressed and mediates TRAIL resistance in human non-small cell lung cancer

Luigi TerraccianoGiulia RomanoNunzia MontuoriDaniel BaumhoerCiro ZancaCarlo BriguoriMichela GarofaloMariarosaria IncoronatoGerolama CondorelliPia RagnoCristina QuintavalleLuigi TornilloMario Acunzo

subject

MaleProgrammed cell deathLung NeoplasmsNecrosisProtein Array AnalysisBiologyTransfectionTNF-Related Apoptosis-Inducing LigandCarcinoma Non-Small-Cell LungCell Line TumormedicineHumansGene silencingRNA Small InterferingLung cancerAgedAged 80 and overTissue microarrayAKTapoptosisIntracellular Signaling Peptides and ProteinsArticlesCell BiologyTransfectionMiddle AgedPhosphoproteinsmedicine.diseaseMolecular biologyRecombinant ProteinsUp-Regulationlung cancerReceptors TNF-Related Apoptosis-Inducing LigandDrug Resistance NeoplasmCell cultureApoptosisMolecular MedicineFemalemedicine.symptomApoptosis Regulatory Proteins

description

PED (phosphoprotein enriched in diabetes) is a death-effector domain (DED) family member with a broad anti-apoptotic action. PED inhibits the assembly of the death-inducing signalling complex (DISC) of death receptors following stimulation. Recently, we reported that the expression of PED is increased in breast cancer cells and determines the refractoriness of these cells to anticancer therapy. In the present study, we focused on the role of PED in non-small cell lung cancer (NSCLC), a tumour frequently characterized by evasion of apoptosis and drug resistance. Immunohistochemical analysis of a tissue microarray, containing 160 lung cancer samples, indicated that PED was strongly expressed in different lung tumour types. Western blotting performed with specimens from NSCLC-affected patients showed that PED was strongly up-regulated (>6 fold) in the areas of tumour compared to adjacent normal tissue. Furthermore, PED expression levels in NSCLC cell lines correlated with their resistance to tumour necrosis factor related apoptosis-inducing ligand (TRAIL)-induced cell death. The involvement of PED in the refractoriness to TRAIL-induced cell death was investigated by silencing PED expression in TRAIL-resistant NSCLC cells with small interfering (si) RNAs: transfection with PED siRNA, but not with cFLIP siRNA, sensitized cells to TRAIL-induced cell death. In conclusion, PED is specifically overexpressed in lung tumour tissue and contributes to TRAIL resistance.

yearjournalcountryeditionlanguage
2008-01-01Journal of Cellular and Molecular Medicine
https://doi.org/10.1111/j.1582-4934.2008.00283.x