Somatostatin inhibits PC Cl3 thyroid cell proliferation through the modulation of phosphotyrosine activity. Impairment of the somatostatinergic effects by stable expression of E1A viral oncogene.
In this study, we report the effects of somatostatin on the proliferation of PC C13 thyroid cell line and the intracellular mechanisms involved. We also evaluated the possible alterations, induced by E1A oncogene transformation on the intracellular pathways mediating somatostatin inhibition of cell proliferation. We showed that somatostatin was able to powerfully inhibit insulin- and insulin + TSH-dependent cell proliferation by inducing a block in the G1/S progression in the cell cycle. These cytostatic effects were completely reverted by vanadate, suggesting that somatostatin may induce antiproliferative effects through the modulation of phosphotyrosine phosphatases. In the E1A-transformed cell line, somatostatin was completely ineffective. The lack of somatostatin inhibitory effects on cell proliferation were not due to alterations in the expression of somatostatin receptors, which were regularly expressed and coupled to adenylyl cyclase activity, but were dependent on an alteration in their coupling with the phosphotyrosine phosphatase. In fact, although in PC C13 cells somatostatin increased by 100% phosphotyrosine phosphatase activity, it was completely ineffective in E1A-expressing cells. In conclusion we demonstrated that somatostatin activates phosphotyrosine phosphatases in PC C13 thyroid cells to inhibit cell proliferation and that the stable expression of E1A oncogene in these cells completely abolishes this antiproliferative effect.
Florio
T
T
Department of Clinical and Experimental Oncology, University of Genoa, Italy.
Scorizello
A
A
Fattore
M
M
D'Alto
V
V
Salzano
S
S
Rossi
G
G
Berlingieri
M T
MT
Fusco
A
A
Schettini
G
G
D017500:Adenovirus E1A Proteins / Q000235:genetics; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015870:Gene Expression; D007328:Insulin / Q000494:pharmacology; D009857:Oncogenes; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D013972:Thyrotropin / Q000494:pharmacology; D014170:Transformation, Genetic; D014638:Vanadates / Q000494:pharmacology
D017500:Adenovirus E1A Proteins; D007328:Insulin; D014638:Vanadates; D013004:Somatostatin; D013972:Thyrotropin; D017027:Protein Tyrosine Phosphatases