The Internalization of Neurotensin by the Low-Affinity Neurotensin Receptors (NTSR2 and vNTSR2) Activates ERK 1/2 in Glioma Cells and Allows Neurotensin-Polyplex Transfection of tGAS1

Cellular and Molecular Neurobiology
Alberto E Ayala-SarmientoJosé Segovia

Abstract

Glioblastoma is the most malignant primary brain tumor and is very resistant to treatment; hence, it has a poor prognosis. Neurotensin receptor type 1 (NTSR1) plays a key role in cancer malignancy and has potential therapeutic applications. However, the presence and function of neurotensin (NTS) receptors in glioblastoma is not clearly established. RT-PCR assays showed that healthy (non-tumor) astroglial cells and C6 glioma cells express NTSR2 and its isoform (vNTSR2) rather than NTSR1. In glioma cells, NTS promotes the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK 1/2), an effect that was completely abolished by blocking the internalization of the NTS/NTSR complex. We demonstrated pharmacologically that the internalization is dependent on the activation of NTSR2 receptors and it was prevented by levocabastine, a NTSR2 receptor antagonist. The internalization of NTSR2 and vNTSR2 was further demonstrated by its ability to mediate gene transfer (transfection) via the NTS-polyplex system. Expression of reporter transgenes and of the pro-apoptotic soluble form of growth arrest specific 1 (tGAS1) was observed in glioma cells. A significant reduction on the viability of C6 cells was determined when tGAS1 was tran...Continue Reading

References

Oct 11, 1992·Annals of Surgery·B M EversJ C Thompson
Feb 1, 1989·The Journal of Cell Biology·J E Heuser, R G Anderson
Aug 1, 1986·Naunyn-Schmiedeberg's Archives of Pharmacology·A SchotteP M Laduron
Feb 18, 1998·International Journal of Cancer. Journal International Du Cancer·A Evdokiou, P A Cowled
Oct 3, 1998·The Journal of Biological Chemistry·J MazellaJ P Vincent
Jul 2, 1999·International Journal of Cancer. Journal International Du Cancer·J C ReubiJ A Laissue
Jul 3, 1999·Trends in Pharmacological Sciences·J P VincentP Kitabgi
Nov 22, 2000·Brain Research. Brain Research Protocols·D Martinez-Fong, I Navarro-Quiroga
Mar 15, 2001·Current Opinion in Cell Biology·W E Miller, R J Lefkowitz
Jun 27, 2002·The Journal of Biological Chemistry·Philippe SarretAlain Beaudet
Aug 2, 2002·Biochemical and Biophysical Research Communications·Sonia SomaïPatricia Forgez
Dec 28, 2002·Journal of Neuroscience Research·Absalom ZamoranoJosé Segovia
May 30, 2006·Biochimica Et Biophysica Acta·Martha L Arango-RodriguezDaniel Martinez-Fong
Jul 13, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Hongtao LvJie Yan
Jul 28, 2006·Peptides·Valérie NavarroJean Mazella
Oct 4, 2006·Molecular Therapy : the Journal of the American Society of Gene Therapy·Juan A Gonzalez-BarriosDaniel Martinez-Fong
Nov 7, 2006·Neuropathology and Applied Neurobiology·S ServotteC Decaestecker
Feb 20, 2007·Annual Review of Physiology·Scott M DeWireSudha K Shenoy
Aug 30, 2007·Proceedings of the National Academy of Sciences of the United States of America·Miriam BreunigAchim Goepferich
Jun 4, 2008·Cancer Research·Omar MoussaDennis K Watson
Nov 5, 2008·Genes & Development·Stephane GobeilMichael R Green
Jan 31, 2009·Cancer Gene Therapy·H A Rubio-ZapataD Martinez-Fong
May 23, 2009·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Gabriela Domínguez-MonzónJosé Segovia
Sep 3, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marco AlifanoPatricia Forgez
Feb 9, 2012·Apoptosis : an International Journal on Programmed Cell Death·Natanael ZarcoJosé Segovia
May 10, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Robert Roskoski
Oct 31, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sofiane SaadaMarie-Odile Jauberteau
May 3, 2013·PloS One·Mónica Díaz-CoránguezLorenza González-Mariscal

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Citations

Dec 31, 2015·Cell and Tissue Research·E EstudilloJ Segovia
May 27, 2016·Histochemistry and Cell Biology·Alberto E Ayala-SarmientoJosé Segovia
May 31, 2017·Clinical and Experimental Pharmacology & Physiology·Qing OuyangLiang Yi
Dec 4, 2020·Cell Death & Disease·Niki ChristouAurélie Perraud
Oct 31, 2020·Molecular Pharmaceutics·Francisco E Lopez-SalasDaniel Martinez-Fong

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