The expression of the phosphotyrosine phosphatase DEP-1/PTPη dictates the responsivity of glioma cells to somatostatin inhibition of cell proliferation

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

Research output: Contribution to journalArticle

Abstract

Here we characterize the intracellular effectors of the antiproliferative activity of somatostatin in glioma cell lines and post-surgical specimens. The responsiveness to somatostatin correlated with the expression of the phosphotyrosine phosphatase DEP-1/PTPη, identified in C6 and U87MG cells, in which somatostatin inhibited cell growth. The expression of a dominant negative mutant of DEP-1/PTPη in C6 cells abolished somatostatin effects, confirming the involvement of this phosphotyrosine phosphatase in such effects. Somatostatin treatment increased the activity of DEP-1/PTPη and inhibited ERK1/2 activation. Conversely, basic fibroblast growth factor-dependent MEK phosphorylation was not affected, suggesting a direct effect on ERK1/2. In vitro experiments showed that PTPη was able to interact and dephosphorylate ERK1/2 activated by basic fibroblast growth factor. Furthermore, by transfecting PTPη in the somatostatin-unresponsive, DEP-1/PTPη-deficient U373MG cells, the somatostatin-dependent control of cell proliferation was recovered. Finally we evaluated the requirement for DEP-1/PTPη in somatostatin inhibition of cell proliferation in post-surgical specimens derived from different grade human gliomas. Although all of the glioma analyzed expressed somatostatin receptor mRNA, DEP-1/PTPη expression was limited to 8 of 22 of the tumors. Culturing seven gliomas, a correlation between the expression of DEP-1/PTPη and the somatostatin antiproliferative effects was identified. In conclusion we propose that the expression and activation of DEP-1/PTPη is required for somatostatin inhibition of glioma proliferation.

Original languageEnglish
Pages (from-to)29004-29012
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number28
DOIs
Publication statusPublished - Jul 9 2004

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Massa, A., Barbieri, F., Aiello, C., Arena, S., Pattarozzi, A., Pirani, P., Corsaro, A., Iuliano, R., Fusco, A., Zona, G., Spaziante, R., Florio, T., & Schettini, G. (2004). The expression of the phosphotyrosine phosphatase DEP-1/PTPη dictates the responsivity of glioma cells to somatostatin inhibition of cell proliferation. Journal of Biological Chemistry, 279(28), 29004-29012. https://doi.org/10.1074/jbc.M403573200