[The activation of the phosphotyrosine phosphatase eta is responsible for the somatostatin inhibition of PCCl3 thyroid cell proliferation].
BACKGROUND
This study was aimed to identify possible intracellular effectors of the somatostatin (SST) antiproliferative activity, in PCCl3 thyroid cells.


METHODS
To prove the involvement of r-PTPeta in SST's effect, we studied th proliferative activity of subclones of PCCl3 cells that do or do not express this PTP.


RESULTS
SST inhibited PCCl3 TSH+insulin-dependent cell proliferation through the induction of a phosphotyrosine phosphatase (PTP) activity, detected using the synthetic substrate pNPP (+150%, p<0.01). Conversely, PCCl3 cells stably expressing the v-mos oncogene (PCmos) were completely insensitive to SST antiproliferative effects due to the incapability of SST to increase PTP activity, that correlated with the abolishment of the expression of the receptor-like PTP, r-PTPeta. In the cells in which r-PTPeta was transfected (PCmos/ PTPeta) SST inhibited cell proliferation showing a dose-dependence similar to that observed in PCCl3 cells. Conversely, the transfection of a catalytically inactive mutant of r-PTPeta did not restore the responsivity to SST. Also in PCmos/PTPeta cells SST, treatment increased membrane PTP activity.


CONCLUSIONS
SST inhibition of PCC13 cell proliferation requires the activation of r-PTPeta.
Florio
T
T
Servizio di Farmacologia e Neuroscienze, IST/CBA, Università degli Studi, Genova, Italy. florio@cba.unige.it
Arena
S
S
Thellung
S
S
Iuliano
R
R
Corsaro
A
A
Massa
A
A
Villa
V
V
Pattarozzi
A
A
Diana
F
F
Fusco
A
A
Schettini
G
G
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects
D006727:Hormone Antagonists; D007527:Isoenzymes; D013004:Somatostatin; D004247:DNA; D017027:Protein Tyrosine Phosphatases; C453859:phosphotyrosine phosphatase eta
L'attivazione della fosfotirosino fosfatasi eta è responsabile dell'inibizione della proliferazione delle cellule tiroidee PCC13 ad opera della somatostatin.