title: The antiapoptotic protein BAG3 is expressed in thyroid carcinomas and modulates apoptosis mediated by tumor necrosis factor-related apoptosis-inducing ligand.
abstract: BACKGROUND
  We previously showed that BAG3 protein, a member of the BAG (Bcl-2-associated athanogene) co-chaperone family, modulates apoptosis in human leukemias. The expression of BAG3 in other tumor types has not been extensively investigated so far.
  
  
  OBJECTIVE
  The objective of this study was to analyze BAG3 expression in thyroid neoplastic cells and investigate its influence in cell apoptotic response to TNF-related apoptosis-inducing ligand (TRAIL).
  
  
  METHODS
  We investigated BAG3 expression in human thyroid carcinoma cell lines, including NPA, and the effect of BAG3-specific small interfering RNA on TRAIL-induced apoptosis in NPA cells. Subsequently, we analyzed BAG3 expression in 30 benign lesions and 56 carcinomas from patients of the Naples Tumor Institute Fondazione Senatore Pascale.
  
  
  METHODS
  The main outcome measures were: analysis of BAG3 protein in NPA cells by Western blot and immunocytochemistry; analysis of apoptosis in TRAIL-stimulated NPA cells by flow cytometry; and evaluation of BAG3 expression in specimens from thyroid lesions by immunohistochemistry.
  
  
  RESULTS
  BAG3 was expressed in human thyroid carcinoma cell lines; small interfering RNA-mediated downmodulation of its levels significantly (P < 0.0195) enhanced NPA cell apoptotic response to TRAIL. The protein was not detectable in 19 of 20 specimens of normal thyroid or goiters, whereas 54 of 56 analyzed carcinomas (15 follicular, 28 papillary, and 13 anaplastic) were clearly positive for BAG3 expression.
  
  
  CONCLUSIONS
  BAG3 downmodulates the apoptotic response to TRAIL in human neoplastic thyroid cells. The protein is specifically expressed in thyroid carcinomas and not in normal thyroid tissue or goiter.
authors.affiliation: Dipartimento di Scienze Farmaceutiche (DiFarma), University of Salerno, Via ponte don Melillo, 84084 Fisciano, Italy. mcturco@unisa.it
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.forename: Massimo
authors.initials: M
authors.lastname: Ammirante
authors.forename: Anna
authors.initials: A
authors.lastname: Basile
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rosati
authors.forename: Michela
authors.initials: M
authors.lastname: Festa
authors.forename: Mario
authors.initials: M
authors.lastname: Monaco
authors.forename: Emilia
authors.initials: E
authors.lastname: Vuttariello
authors.forename: Rosa
authors.initials: R
authors.lastname: Pasquinelli
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Monica
authors.initials: M
authors.lastname: Zerilli
authors.forename: Matilde
authors.initials: M
authors.lastname: Todaro
authors.forename: Giorgio
authors.initials: G
authors.lastname: Stassi
authors.forename: Luciano
authors.initials: L
authors.lastname: Pezzullo
authors.forename: Antonio
authors.initials: A
authors.lastname: Gentilella
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tosco
authors.forename: Maria
authors.initials: M
authors.lastname: Pascale
authors.forename: Liberato
authors.initials: L
authors.lastname: Marzullo
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Belisario
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Turco
authors.forename: Arturo
authors.initials: A
authors.lastname: Leone
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D034741:RNA, Small Interfering / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D034741:RNA, Small Interfering; D053221:TNF-Related Apoptosis-Inducing Ligand