SPARC overexpression suppresses radiation-induced HSP27 and induces the collapse of mitochondrial Δψ in neuroblastoma cells

Tanpure,Smita; Boyineini,Jerusha; Gnanamony,Manu; Antony,Reuben; Fernández,Karen  S.; Libes,Jaime; Lin,Julian; Pinson,David; Joseph,Pushpa  A.; Gondi,Christopher  S.

doi:10.3892/ol.2017.6075

SPARC overexpression suppresses radiation-induced HSP27 and induces the collapse of mitochondrial Δψ in neuroblastoma cells

Authors:
- Smita Tanpure
- Jerusha Boyineini
- Manu Gnanamony
- Reuben Antony
- Karen S. Fernández
- Jaime Libes
- Julian Lin
- David Pinson
- Pushpa A. Joseph
- Christopher S. Gondi
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Affiliations: Department of Internal Medicine, University of Illinois College of Medicine, Peoria, IL 61605, USA, Department of Pediatrics, University of Illinois College of Medicine, Peoria, IL 61605, USA, Department of Neurosurgery, University of Illinois College of Medicine, Peoria, IL 61605, USA, Department of Pathology, University of Illinois College of Medicine, Peoria, IL 61605, USA
Published online on: April 24, 2017 https://doi.org/10.3892/ol.2017.6075
Pages: 4602-4610
Copyright: © Tanpure et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Neuroblastoma is the cause of >15% of cancer-associated mortality in children in the USA. Despite aggressive treatment regimens, the long‑term survival rate for these children remains at <40%. The current study demonstrates that secreted protein acidic and rich in cysteine (SPARC) suppresses radiation‑induced expression of heat shock protein 27 (HSP27) in vivo and suppresses mitochondrial membrane potential (Δψ) in neuroblastoma cells. In the present study, the overexpression of SPARC in SK‑N‑BE(2) and NB1691 neuroblastoma cell lines suppresses radiation‑induced G2M cell cycle arrest, proliferation, HSP27 expression (in vitro and in vivo) and induces the collapse of the mitochondrial Δψ. Gene ontology analysis demonstrated that the overexpression of SPARC combined with irradiation, induces the expression of dissimilar molecular function genes in SK‑N‑BE(2) and NB1691 cells, providing evidence of a dissimilar response signaling pathway. These results demonstrate that overexpression of SPARC suppresses radiation‑induced HSP27 expression in neuroblastoma cells and the combination of SPARC and radiation induces the expression of protein 21, but suppresses neuroblastoma tumor density in in vivo mouse models. SPARC also induces mitochondrial Δψ collapse in SK‑N‑BE(2) and NB1691 neuroblastoma cells.

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