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

Gennaro Chiappetta, Anna Basile, Antonio 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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6846-6853
Number of pages8
JournalOncotarget
Volume5
Issue number16
Publication statusPublished - 2014

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Apoptosis Regulatory Proteins
Small Cell Lung Carcinoma
Carcinoma
Lung
Growth
Neoplasms
Small Interfering RNA
Cisplatin
Down-Regulation
Large Cell Carcinoma
Heterografts
Adenoviridae
Squamous Cell Carcinoma
Cell Survival
Adenocarcinoma
Cell Death
Immunohistochemistry
Apoptosis
Drug Therapy
Cell Line

Keywords

  • Apoptosis
  • BAG3
  • NSCLC
  • SCLC
  • Tumor growth

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this

The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth. / Chiappetta, Gennaro; Basile, Anna; Barbieri, Antonio; Falco, Antonia; Rosati, Alessandra; Festa, Michelina; Pasquinelli, Rosa; Califano, Daniela; Palma, Giuseppe; Costanzo, Raffaele; Barcaroli, Daniela; Capunzo, Mario; Franco, Renato; Rocco, Gaetano; Pascale, Maria; Turco, Maria Caterina; De Laurenzi, Vincenzo; Arra, Claudio.

In: Oncotarget, Vol. 5, No. 16, 2014, p. 6846-6853.

Research output: Contribution to journalArticle

Chiappetta, G, Basile, A, Barbieri, A, Falco, A, Rosati, A, Festa, M, Pasquinelli, R, Califano, D, Palma, G, Costanzo, R, Barcaroli, D, Capunzo, M, Franco, R, Rocco, G, Pascale, M, Turco, MC, De Laurenzi, V & Arra, C 2014, 'The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth', Oncotarget, vol. 5, no. 16, pp. 6846-6853.
Chiappetta, Gennaro ; Basile, Anna ; Barbieri, Antonio ; Falco, Antonia ; Rosati, Alessandra ; Festa, Michelina ; Pasquinelli, Rosa ; Califano, Daniela ; Palma, Giuseppe ; Costanzo, Raffaele ; Barcaroli, Daniela ; Capunzo, Mario ; Franco, Renato ; Rocco, Gaetano ; Pascale, Maria ; Turco, Maria Caterina ; De Laurenzi, Vincenzo ; Arra, Claudio. / The anti-apoptotic BAG3 protein is expressed in lung carcinomas and regulates small cell lung carcinoma (SCLC) tumor growth. In: Oncotarget. 2014 ; Vol. 5, No. 16. pp. 6846-6853.
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