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/PTPeta, identified in C6 and U87MG cells, in which somatostatin inhibited cell growth. The expression of a dominant negative mutant of DEP-1/PTPeta in C6 cells abolished somatostatin effects, confirming the involvement of this phosphotyrosine phosphatase in such effects. Somatostatin treatment increased the activity of DEP-1/PTPeta 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 PTPeta was able to interact and dephosphorylate ERK1/2 activated by basic fibroblast growth factor. Furthermore, by transfecting PTPeta in the somatostatin-unresponsive, DEP-1/PTPeta-deficient U373MG cells, the somatostatin-dependent control of cell proliferation was recovered. Finally we evaluated the requirement for DEP-1/PTPeta 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/PTPeta expression was limited to 8 of 22 of the tumors. Culturing seven gliomas, a correlation between the expression of DEP-1/PTPeta and the somatostatin antiproliferative effects was identified. In conclusion we propose that the expression and activation of DEP-1/PTPeta is required for somatostatin inhibition of glioma proliferation.
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|Titolo:||The expression of the phosphotyrosine phosphatase DEP-1/PTPeta dictates the responsivity of glioma cells to somatostatin inhibition of cell proliferation|
|Data di pubblicazione:||2004|
|Citazione:||The expression of the phosphotyrosine phosphatase DEP-1/PTPeta dictates the responsivity of glioma cells to somatostatin inhibition of cell proliferation / Massa, A.; Barbieri, Federica; Aiello, C.; Arena, S.; Pattarozzi, Alessandra; Pirani, P.; Corsaro, Alessandro; Iuliano, R.; Fusco, A.; Zona, Gianluigi; Spaziante, R.; Florio, Tullio; Schettini, Gennaro. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 279(2004), pp. 29004-29012.|
|Appare nelle tipologie:||01.01 - Articolo su rivista|