The phosphotyrosine phosphatase η mediates somatostatin inhibition of glioma proliferation via the dephosphorylation of ERK1/2

Alessandro Massa, Federica Barbieri, Cinzia Aiello, Rodolfo Iuliano, Sara Arena, Alessandra Pattarozzi, Alessandro Corsaro, Valentina Villa, Alfredo Fusco, Gianluigi Zona, Renato Spaziante, Gennaro Schettini, Tullio Florio

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Abstract

Somatostatin (SST) controls the proliferation of a variety of cell types. Its effects are mediated by five G protein-coupled receptors (SSTR1-SSTR5), variably expressed in normal and cancer tissues. SST inhibition of cell proliferation can be exploited by both direct and indirect mechanisms: the main direct pathway involves the modulation of phosphotyrosine phosphatase (PTP) activity. Here we show that SST cytostatic activity is mediated by the activation of a receptor-like PTP, named PTPη. The role of this PTP in the antiproliferative activity of SST in five glioma cell lines (C6, U87MG, U373MG, DBTRG05MG, and CAS1) and in four postsurgical human glioblastoma specimens, has been studied. SST inhibited growth only in C6 and U87MG that express PTPη. In C6 cells, SST antiproliferative effects were reverted by pretreatment with pertussis toxin and vanadate, indicating the involvement of G proteins and PTPs. The role of PTPη in the SST inhibitory effects was demonstrated by testing the PTPη activity: it was increased by SST treatment and paralleled by inhibition of ERK1/2 activation. Since basic fibroblast growth factor-dependent MEK phosphorylation was not affected by SST, we propose a direct effect of SST-activated PTPη on ERK1/2 phosphorylation. Finally, the SSTR mRNAs were identified in all of the 36 gliomas analyzed, whereas PTPη expression was found in 33% of cases. Culturing four gliomas, a precise correlation between the expression of PTPη and the SST antiproliferative effects was identified. In conclusion, in glioma cells, SST antiproliferative activity requires the expression and activation of PTPη, which directly dephosphorylates ERK1/2.

Original languageEnglish
Pages (from-to)264-274
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume1030
DOIs
Publication statusPublished - 2004

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Keywords

  • Cell proliferation
  • Human brain tumors
  • Phosphotyrosine phosphatases
  • Somatostatin
  • Somatostatin receptors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Massa, A., Barbieri, F., Aiello, C., Iuliano, R., Arena, S., Pattarozzi, A., Corsaro, A., Villa, V., Fusco, A., Zona, G., Spaziante, R., Schettini, G., & Florio, T. (2004). The phosphotyrosine phosphatase η mediates somatostatin inhibition of glioma proliferation via the dephosphorylation of ERK1/2. Annals of the New York Academy of Sciences, 1030, 264-274. https://doi.org/10.1196/annals.1329.033