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The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth

2014; Impact Journals LLC; Volume: 5; Issue: 16 Linguagem: Inglês

10.18632/oncotarget.2261

1949-2553

Gennaro Chiappetta, Anna Basile, Antônio Barbieri, Antonia Falco, Alessandra Rosati, Michelina Festa, Rosa Pasquinelli, Daniela Califano, Giuseppe Palma, Raffaele Costanzo, Daniela Barcaroli, Mario Capunzo, Renato Franco, Gaetano Rocco, Maria Pascale, Maria Caterina Turco, Vincenzo De Laurenzi, Claudio Arra,

Neuroendocrine Tumor Research Advances

// Gennaro Chiappetta 1,* , Anna Basile 2,3,* , Antonio Barbieri 4 , Antonia Falco 2,3 , Alessandra Rosati 2,3 , Michelina Festa 2,3 , Rosa Pasquinelli 1 , Daniela Califano 1 , Giuseppe Palma 4 , Raffaele Costanzo 5 , Daniela Barcaroli 6 , Mario Capunzo 7 , Renato Franco 8 , Gaetano Rocco 9 , Maria Pascale 2,3 , Maria Caterina Turco 3,7 , Vincenzo De Laurenzi 3,6 and Claudio Arra 4 1 Functional Genomic Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy 2 Department of Pharmacy, University of Salerno, Fisciano, Italy 3 BIOUNIVERSA S.r.l., University of Salerno, Fisciano, Italy 4 Animal Facility Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy 5 Medical Oncology Unit, Thoraco-Pulmonary Department, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy 6 Department of Experimental and Clinical Sciences, University G. D'Annunzio and Fondazione G. D'Annunzio, Ce.S.I., Chieti, Italy 7 Department of Medicine and Surgery, University of Salerno, Fisciano, Italy 8 Pathology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy 9 Thoracic Surgery Unit, Thoraco-Pulmonary Department, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy * These Authors contributed equally to the work Correspondence: Maria Caterina Turco, email: // Keywords : BAG3, SCLC, NSCLC, tumor growth, apoptosis Received : July 08, 2014 Accepted : July 25, 2014 Published : July 25, 2014 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.