SPARC overexpression inhibits cell proliferation in neuroblastoma and is partly mediated by tumor suppressor protein PTEN and AKT.

PloS One
Praveen BhoopathiJasti S Rao

Abstract

Secreted protein acidic and rich in cysteine (SPARC) is also known as BM-40 or Osteonectin, a multi-functional protein modulating cell-cell and cell-matrix interactions. In cancer, SPARC is not only linked with a highly aggressive phenotype, but it also acts as a tumor suppressor. In the present study, we sought to characterize the function of SPARC and its role in sensitizing neuroblastoma cells to radio-therapy. SPARC overexpression in neuroblastoma cells inhibited cell proliferation in vitro. Additionally, SPARC overexpression significantly suppressed the activity of AKT and this suppression was accompanied by an increase in the tumor suppressor protein PTEN both in vitro and in vivo. Restoration of neuroblastoma cell radio-sensitivity was achieved by overexpression of SPARC in neuroblastoma cells in vitro and in vivo. To confirm the role of the AKT in proliferation inhibited by SPARC overexpression, we transfected neuroblastoma cells with a plasmid vector carrying myr-AKT. Myr-AKT overexpression reversed SPARC-mediated PTEN and increased proliferation of neuroblastoma cells in vitro. PTEN overexpression in parallel with SPARC siRNA resulted in decreased AKT phosphorylation and proliferation in vitro. Taken together, these r...Continue Reading

References

Jan 10, 1980·Nature·G Poste, I J Fidler
Nov 13, 1998·Science·M H CardoneJ C Reed
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·L C Cantley, B G Neel
Nov 24, 1999·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Q Yan, E H Sage
Dec 10, 1999·Nature Cell Biology·M G Vander Heiden, C B Thompson
Oct 24, 2000·Clinical and Experimental Dermatology·P Kurschat, C Mauch
Mar 29, 2001·Critical Reviews in Eukaryotic Gene Expression·M H WeberF W Orr
May 9, 2002·Molecular and Cellular Biology·Bangyan StilesHong Wu
Feb 11, 2003·Journal of Cellular Biochemistry·Aleksandar FranckiE Helene Sage
Feb 18, 2003·The Journal of Clinical Investigation·Rolf A BrekkenE Helene Sage
Aug 30, 2003·Oncogene·George IliakisHuichen Wang
Jan 31, 2004·International Journal of Radiation Oncology, Biology, Physics·Zhaomei MuAlan Pollack
Mar 23, 2004·Journal of Cellular Biochemistry·Aleksandar FranckiE Helene Sage
Nov 19, 2004·Nature·Michael B Kastan, Jiri Bartek
Dec 2, 2004·Cell Motility and the Cytoskeleton·Tony YeungPaul A Janmey
May 20, 2005·The Journal of Clinical Investigation·Isabella T TaiLan Bo Chen
Nov 19, 2005·Science·Dennis E DischerYu-Li Wang
Nov 30, 2005·The American Journal of Pathology·Neveen Said, Kouros Motamed
Feb 10, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Courtney A GranvillePhillip A Dennis
Jun 14, 2006·Cancer Metastasis Reviews·Dave S B HoonKlaus Pantel
Apr 20, 2007·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Li WangQin-Long Li
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Feb 7, 2008·Journal of Cellular Biochemistry·Clancy J Clark, E Helene Sage
May 7, 2008·Cancer Metastasis Reviews·Osvaldo L PodhajcerAndrea S Llera
Jun 11, 2008·Cancer Metastasis Reviews·Osvaldo L PodhajcerAndrea S Llera

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Citations

Feb 6, 2013·Expert Opinion on Therapeutic Patents·Chandra S Boosani, Devendra K Agrawal
Jan 17, 2017·Developmental Biology·Paula IrlesMaria-Dolors Piulachs
Apr 30, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marzena CydzikJean Gariépy

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Methods Mentioned

BETA
nuclear translocation
X-ray
FACS
transfection
flow cytometry
xenografts
PCR

Software Mentioned

Cell Quest
Imgenex

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