Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The somatostatin receptor subtype sst2 mediates both activation of a tyrosine phosphatase activity and inhibition of cell proliferation induced by somatostatin analogues. In the absence of exogenous ligand, expression of sst2 in NIH 3T3 cells resulted in inhibition of cell growth. Polymerase chain reaction coupled to reverse transcription demonstrated that expression of sst2 in NIH 3T3 cells stimulated the expression of preprosomatostatin mRNA accompanied by a production of immunoreactive somatostatin-like peptide which corresponded predominantly to somatostatin 14. Moreover anti-somatostatin antibodies suppressed sst2-promoted inhibition of cell proliferation. Inhibition of cell proliferation associated with increased secretion of somatostatin-like immunoreactivity was also observed after expression of sst2 in human pancreatic tumor cells BxPC3 devoid of endogenous receptors. In addition, expression of sst2 in NIH 3T3 cells was associated with constitutive activation of tyrosine phosphatase PTP1C that resulted from enhanced expression of the protein. Blocking of PTP1C tyrosine phosphatase activity with orthovanadate or that of PTP1C protein with antisense PTP1C oligonucleotides decreased the sst2-induced inhibition of cell proliferation. These results, taken together, show that expression of sst2 in NIH 3T3 cells generated a negative autocrine loop by stimulating sst2 ligand production and amplifying PTP1C sst2-transducer. Sst2/ligand may function as a determinant factor involved in the negative growth control of cells.
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PMID:Induction of a negative autocrine loop by expression of sst2 somatostatin receptor in NIH 3T3 cells. 862 71

Somatostatin (SST) analogs exert direct antiproliferative actions in pancreatic, pituitary, and mammary tumor cells in vitro. SST receptor (SSTR)-mediated induction of membrane-associated protein tyrosine phosphatase (PTP) activity has been implicated in its anti-proliferative signaling by virtue of its ability to dephosphorylate and inactivate growth factor receptor kinases. Recently, a PTP-containing Src homology 2 domain, identified as PTP1C/SHPTP1/SHP/HCP, was found to be associated with SSTR in rat pancreatic acinar cell membranes. In the present study we investigated the antiproliferative action of the octapeptide SST analog SMS 201-995 (OCT) and its effect on PTP activity in MCF-7 human breast adenocarcinoma cells. We report here that OCT does not directly stimulate membrane-associated PTP activity, but induces translocation of intracellular PTP to the membrane in MCF-7 cells preincubated with the peptide in a time- and concentration-dependent manner. We demonstrate that this is due at least in part to OCT-induced recruitment of cytosolic PTP1C. OCT-induced recruitment of PTP1C to the cell surface as well as its ability to inhibit the growth of MCF-7 cells was G protein dependent and inhibited by orthovanadate. These findings suggest that translocation of cytosolic PTP1C by SST analogs to the cell surface is an early event in its antiproliferative signaling in tumor cells.
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PMID:Octapeptide somatostatin analog SMS 201-995 induces translocation of intracellular PTP1C to membranes in MCF-7 human breast adenocarcinoma cells. 875 75

A protein of 66 kd immunoreactive to anti-tyrosine phosphatase (PTP1C) antibodies coeluted with, and so may be associated with, somatostatin receptors (ssts) from rat pancreatic membranes. Also, anti-PTP1C antibodies immunoprecipitated functional ssts from pancreatic membranes, suggesting a PTP1C protein can associate with ssts at the membrane level. Somatostatin analog RC 160 had good affinity for sst2,3 and sst5 (IC50 = 0.2, 0.1, and 21 nmol/L) and low affinity for sst1 and sst4 (IC50 = 200 and 620 nmol/L), and induced rapid dose-dependent stimulation of PTP activity (maximal at 1 nmol/L and half maximal at 5 pmol/L) in NIH3T3 and CHO cells expressing sst2, with similar results for sst1, but no stimulation with sst3,4 or sst5. Treatment of cells expressing sst2 with RC 160 for 24 hours inhibited serum- or growth factor-induced cell proliferation dose-dependently (maximal at 1 nmol/L, half maximal at 6 to 53 pmol/L RC 160). In cells expressing sst1, weak inhibition of fibroblast growth factor 2-induced NIH3T3 cell proliferation was provoked by somatostatin analogs (> 10 nmol/L). The good correlation between inhibition of somatostatin binding, stimulation of PTP activity, and inhibition of cell proliferation implicates a PTP in growth inhibition mediated by sst2 and sst1.
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PMID:Molecular mechanisms of antiproliferative effect of somatostatin: involvement of a tyrosine phosphatase. 876 71

Somatostatin (SS-14) and its structural analogue SMS 201-995 (SMS) are recognized as physiological inhibitors of multiple organs and tissue functions through specific membrane receptors (sst1-sst5). The effects of SS-14 and SMS in the growth control of the pancreatic cancer cell lines MIA PaCa-2 and PANC-1 were investigated to identify and clarify the intracellular events involved. In PANC-1 cells, SS-14 and SMS caused inhibition of their basal growth, and that stimulated by epidermal growth factor, with a maximal effect at 0.1-1 microM. To understand the inhibitory mechanisms, we investigated the effects of SS-14 and SMS on phosphotyrosine phosphatase (PTPase) activity and, more specifically, that of tyrosine phosphatase SHP-1 (PTP1C). SS-14 and SMS caused significant increases in total cellular PTPase activity, and particularly SHP-1, with maximal activation within 1 min. Inhibition of membrane tyrosine kinase and p42 MAP kinase activities was also observed, in response to SS-14 and SMS. In MIA PaCa-2 cells, SS-14 and SMS were associated with a positive growth response at 1-10 nM, after 4 days of culture in serum-free medium. Total cellular PTPase activity was slightly increased, but SHP-1 activity could not be detected; its absence in this cell line was confirmed by Western blot. Membrane tyrosine kinase activities were significantly increased by SS-14 and SMS at concentrations needed for maximal growth. p44/p42, which are constitutively active in this cell line, and p38 activities were not affected by somatostatin. In conclusion, somatostatin can exert different effects on human pancreatic cancer cell growth, depending upon the presence or absence of SHP-1. This enzyme can play a key role in the control of cell proliferation, and its cellular presence may determine the therapeutic potential of somatostatin in the control of cancer cell growth.
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PMID:Inhibitory and stimulatory effects of somatostatin on two human pancreatic cancer cell lines: a primary role for tyrosine phosphatase SHP-1. 992 4