title: The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth.
abstract: BAG3, member the HSP70 co-chaperones family, has been shown to play a relevant role in the survival, growth and invasiveness of different tumor types. In this study, we investigate the expression of BAG3 in 66 specimens from different lung tumors and the role of this protein in small cell lung cancer (SCLC) tumor growth. Normal lung tissue did not express BAG3 while we detected the expression of BAG3 by immunohistochemistry in all the 13 squamous cell carcinomas, 13 adenocarcinomas and 4 large cell carcinomas. Furthermore, we detected BAG3 expression in 22 of the 36 SCLCs analyzed. The role on SCLC cell survival was determined by down-regulating BAG3 levels in two human SCLC cell lines, i.e. H69 and H446, in vitro and measuring cisplatin induced apoptosis. Indeed down-regulation of BAG3 determines increased cell death and sensitizes cells to cisplatin treatment. The effect of BAG3 down-regulation on tumor growth was also investigated in an in vivo xenograft model by treating mice with an adenovirus expressing a specific bag3 siRNA. Treatment with bag3 siRNA-Ad significantly reduced tumor growth and improved animal survival. In conclusion we show that a subset of SCLCs over express BAG3 that exerts an anti-apoptotic effect resulting in resistance to chemotherapy.
authors.affiliation: Functional Genomic Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy. .
authors.forename: Gennaro
authors.initials: G
authors.lastname: Chiappetta
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy. BIOUNIVERSA S.r.l., University of Salerno, Fisciano, Italy. .
authors.forename: Anna
authors.initials: A
authors.lastname: Basile
authors.affiliation: Animal Facility Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Barbieri
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy. BIOUNIVERSA S.r.l., University of Salerno, Fisciano, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Falco
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy. BIOUNIVERSA S.r.l., University of Salerno, Fisciano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rosati
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy. .
authors.forename: Michelina
authors.initials: M
authors.lastname: Festa
authors.affiliation: Functional Genomic Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Pasquinelli
authors.affiliation: Functional Genomic Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Califano
authors.affiliation: Animal Facility Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palma
authors.affiliation: Medical Oncology Unit, Thoraco-Pulmonary Department, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Costanzo
authors.affiliation: Department of Experimental and Clinical Sciences, University G. D'Annunzio and Fondazione G. D'Annunzio, Ce.S.I., Chieti, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Barcaroli
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Fisciano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Capunzo
authors.affiliation: Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.affiliation: Thoracic Surgery Unit, Thoraco-Pulmonary Department, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Rocco
authors.affiliation: Department of Pharmacy, University of Salerno, Fisciano, Italy. BIOUNIVERSA S.r.l., University of Salerno, Fisciano, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pascale
authors.affiliation: BIOUNIVERSA S.r.l., University of Salerno, Fisciano, Italy. Department of Medicine and Surgery, University of Salerno, Fisciano, Italy.
authors.forename: Maria Caterina
authors.initials: MC
authors.lastname: Turco
authors.affiliation: BIOUNIVERSA S.r.l., University of Salerno, Fisciano, Italy. Department of Experimental and Clinical Sciences, University G. D'Annunzio and Fondazione G. D'Annunzio, Ce.S.I., Chieti, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Laurenzi
authors.affiliation: Animal Facility Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C498806:Bag3 protein, mouse; D002945:Cisplatin