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

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 - Oncotarget (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Functional Genomic Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy. .

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.

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Immunohistochemical analysis of BAG3 expression in normal and neoplastic lung samplesParaffin sections from 33 NSCLCs, 36 SCLCs and 3 normal lung specimens were analyzed by immunohistochemistry using anti-BAG3 rabbit polyclonal antibody. A) Normal lung tissue sample showing no immunoreactivity for BAG3 (200x). B) Lung adenocarcinoma showing BAG3 cytoplasmic staining (200x). C) Squamous cell carcinoma sample showing cytoplasmic BAG3 staining (200x). D) Immunostaining of the same squamous cell carcinoma sample as in panel C stained without the primary antibody (200x). E) SCLC sample showing BAG3 cytoplasmic staining (200x). F) SCLC sample negative for BAG3 protein expression (200x).
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Figure 1: Immunohistochemical analysis of BAG3 expression in normal and neoplastic lung samplesParaffin sections from 33 NSCLCs, 36 SCLCs and 3 normal lung specimens were analyzed by immunohistochemistry using anti-BAG3 rabbit polyclonal antibody. A) Normal lung tissue sample showing no immunoreactivity for BAG3 (200x). B) Lung adenocarcinoma showing BAG3 cytoplasmic staining (200x). C) Squamous cell carcinoma sample showing cytoplasmic BAG3 staining (200x). D) Immunostaining of the same squamous cell carcinoma sample as in panel C stained without the primary antibody (200x). E) SCLC sample showing BAG3 cytoplasmic staining (200x). F) SCLC sample negative for BAG3 protein expression (200x).

Mentions: We analyzed BAG3 expression in 69 samples (36 small cell lung cancers, 13 squamous cell carcinomas, 13 adenocarcinomas, 4 large cell carcinomas and 3 normal lung samples as control) by immunoistochemistry (IHC), using an anti-BAG3 polyclonal antibody (TOS-2). As expected no BAG3 expression was detected in normal lung while all the NSCLC and 22 out of the 36 SCLC samples were BAG3- positive (Table 1 and Fig.1). Positive tumor samples showed a cytoplasmic staining in the majority of the cells.


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

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 - Oncotarget (2014)

Immunohistochemical analysis of BAG3 expression in normal and neoplastic lung samplesParaffin sections from 33 NSCLCs, 36 SCLCs and 3 normal lung specimens were analyzed by immunohistochemistry using anti-BAG3 rabbit polyclonal antibody. A) Normal lung tissue sample showing no immunoreactivity for BAG3 (200x). B) Lung adenocarcinoma showing BAG3 cytoplasmic staining (200x). C) Squamous cell carcinoma sample showing cytoplasmic BAG3 staining (200x). D) Immunostaining of the same squamous cell carcinoma sample as in panel C stained without the primary antibody (200x). E) SCLC sample showing BAG3 cytoplasmic staining (200x). F) SCLC sample negative for BAG3 protein expression (200x).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4196167&req=5

Figure 1: Immunohistochemical analysis of BAG3 expression in normal and neoplastic lung samplesParaffin sections from 33 NSCLCs, 36 SCLCs and 3 normal lung specimens were analyzed by immunohistochemistry using anti-BAG3 rabbit polyclonal antibody. A) Normal lung tissue sample showing no immunoreactivity for BAG3 (200x). B) Lung adenocarcinoma showing BAG3 cytoplasmic staining (200x). C) Squamous cell carcinoma sample showing cytoplasmic BAG3 staining (200x). D) Immunostaining of the same squamous cell carcinoma sample as in panel C stained without the primary antibody (200x). E) SCLC sample showing BAG3 cytoplasmic staining (200x). F) SCLC sample negative for BAG3 protein expression (200x).
Mentions: We analyzed BAG3 expression in 69 samples (36 small cell lung cancers, 13 squamous cell carcinomas, 13 adenocarcinomas, 4 large cell carcinomas and 3 normal lung samples as control) by immunoistochemistry (IHC), using an anti-BAG3 polyclonal antibody (TOS-2). As expected no BAG3 expression was detected in normal lung while all the NSCLC and 22 out of the 36 SCLC samples were BAG3- positive (Table 1 and Fig.1). Positive tumor samples showed a cytoplasmic staining in the majority of the cells.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Functional Genomic Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", IRCCS, Naples, Italy. .

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.

Show MeSH
Related in: MedlinePlus