UNIPROT:P61278 - FACTA Search

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AIM:To explore the effect and mechanism of gastrin and its antagonists prog lumide and somatostatin on colorectal carcinoma and their clinical significance.METHODS:A model of transplanted human colonic carcinoma was established from SW480 cell line in gymnomouse body.The volume and weight of transplanted carcinoma was observed under the effect of pentagatrin (PG), proglumide (PGL) and octapeptide somotostatin (SMS201-995, SMS). The cAMP content of carcinoma cell was determined by radioimmunoassay and the DNA, protein content and cell cycle were determined by flow-cytometry. The amount of viable cells was determined by MTT colorimetric analysis,IP(3) content was determined by radioimmunoassay, Ca(2+) concentration in cell by fluorometry and PKC activity by isotopic enzymolysis. The expression of gastrin, c-myc, c-fos and rasP21 in 48 cases of colorectal carcinoma tissue was detected by the immuno-cytochemistry SP method. Argyrophilia nucleolar organizer regions was determined with argyrophilia stain.RESULTS:The volume,weight, cAMP, DNA and protein content in carcinoma cell, cell amount and proliferation index of S and G(2)M phase in PG group were all significantly higher than those of control group. When PG was at the concentration of 25mg/L, the amount of viable cells, IP(3) content and Ca(2+) concentration in cell and membrane PKC activity in PG group were significantly higher than those in control group; when PGL was at a concentration of 32mg/L, they dropped to the lowest level in PG (25mg/L)+PGL group, but without significant difference from the control group. The positive expression rate of gastrin, c-myc, c-fos and rasP21 in carcinoma tissue was 39.6%, 54.2%, 47.9% and 54.2% respectively and significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa. The positive expression rate of gastrin of highly differentiated adenocarcinoma group was significantly higher than that of poorly differentiated and mucinous adenocar-cinoma groups. The AgNORs count of carcinoma tissue was significantly higher than that in mucosa 3cm and 6cm adjacent to carcinoma tissue and normal colorectal mucosa; and the positive expression of c-myc and c-fos and the AgNORs count in gastrin-positive group was significantly higher than those in gastrin negative group.CONCLUSION:Pentagastrin has a promoting effect on the growth of transplanted human colonic carcinoma from SW480 cell line. PGL has no obvious effect on the growth of human colonic carcinoma SW480 cell line, but could inhibit the growth promoting effect of PG on transplanted carcinoma. Somatostatin can not only inhibit the growth of transplanted human colonic carcinoma from SW480 cell line directly but also depress the growth-promoting effect of gastrin on the transplanted carcinoma. Some colorectal carcinoma cells can produce and secrete gastrin through autocrine, highly differentiated adenocarcinoma express the highest level gastrin.Endogenous gastrin can stimulate the cell division and proliferation of carcinoma cell and promote the growth of colorectal carcinoma regulating the expression of oncogene c-myc, c-fos. Our study has provided experimental basis for the adjuvant treatment using gastrin antagonist such as PGL, somatostatin of patients with colorectal carcinoma.
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PMID:Regulatory effect and mechanism of gastrin and its antagonists on colorectal carcinoma. 1181 78

Vasoactive intestinal peptide (VIP) stimulates the proliferation and invasiveness of malignant prostatic cells. Receptors for VIP and the closely related growth hormone-releasing hormone (GH-RH) show considerable homology and are found in prostatic and other carcinomas. Among various analogs of GH-RH synthesized, JV-1-52 is a non-selective VIP/GH-RH antagonist, whereas JV-1-53 is a VIP antagonist devoid of GH-RH antagonistic effect. In our study, nude mice bearing PC-3 human androgen-independent prostate carcinomas were treated with JV-1-52 or JV-1-53 (20 microg/day, s.c.) for 28 days. Both antagonists produced a similar reduction in tumor volume (62-67%, p < 0.01) and tumor weight (59-62%; p < 0.05) vs. controls and extended tumor doubling-time from 9.1 to about 16 days (p < 0.05). To investigate the mechanisms involved, in another study we compared the effects of JV-1-53 with those of somatostatin analog RC-160. VIP antagonist JV-1-53 reduced tumor weight by 67% (p < 0.01) and suppressed the expression of mRNA for c-fos and c-jun oncogenes by about 34% (p < 0.05), without affecting serum levels of insulin-like growth factor-I (IGF-I). In contrast, RC-160 (50 microg/day) reduced serum IGF-I by 19% (p < 0.05), but did not significantly decrease tumor weight. mRNA for VIP and high affinity receptors for VIP were detected on PC-3 tumors. Our results suggest that VIP/GH-RH antagonists can inhibit the growth of androgen-independent prostate cancer by abrogating the autocrine/paracrine mitogenic stimuli of VIP. The ability of GH-RH antagonists to block tumoral VIP receptors, in addition to GH-RH receptors, could be potentially beneficial for prostate cancer therapy.
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PMID:Inhibition of PC-3 human prostate cancers by analogs of growth hormone-releasing hormone (GH-RH) endowed with vasoactive intestinal peptide (VIP) antagonistic activity. 1192 Jun 25

In the present study, the effect of ACTH on the expression of somatostatin and c-fos in the spinal cord and formalin induced pain responses in rats were studied using immunohistochemistry and in situ hybridization. The results showed that subcutaneous injection of formalin in the right hindpaw increased c-fos-like immunoreactivity (FLI), somatostatin-like immunoreactivity (Som-LI), Som-LI/FLI and perprosomatostatin mRNA (PPS-mRNA) in neurones of right spinal dorsal horn and significantly enhanced pain intensity rating. ACTH decreased the FLI,Som-LI, Som-LI/FLI and PPS-mRNA levels of the spinal cord evoked by formalin. The decrease of c-fos or Som level due to intrathecal injection of ACTH in rats with chronic pain was prevented by injection of cyproheptadine, but not by bicuculline and naloxone. The results indicate that the serotonin receptor may be involved in ACTH induced analgesia.
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PMID:[Effect of ACTH on the expression of somatostatin and c-fos in the spinal cord and formalin evoked pain response]. 1197 77

Pituitary gland growth hormone (GH) secretion is influenced by two hypothalamic neuropeptides: growth hormone-releasing hormone (GHRH) and somatostatin. Recent data also suggest that estrogen modulates GH release, particularly at the time of the preovulatory luteinizing hormone surge, when a coincident surge of GH is observed in sheep. The GHRH neurons do not possess estrogen receptor alpha (ERalpha), suggesting that estrogen does not act directly on GHRH neurons. Similarly, few somatotropes express ERalpha, suggesting a weak pituitary effect of estradiol on GH. It was hypothesized, therefore, that estradiol may affect somatostatin neurons to modulate GH release from the pituitary. Using immunocytochemical approaches, the present study revealed that although somatostatin neurons were located in several hypothalamic sites, only those in the arcuate nucleus (13% +/- 2%) and ventromedial nucleus (VMN; 29% +/- 1%) expressed ERalpha. In addition, we found that all neurons immunoreactive for somatostatin-14 were also immunoreactive for somatostatin-28(1-12). To determine whether increased GH secretion in response to estradiol is through modulation of GHRH and/or somatostatin neuronal activity, a final study investigated whether c-fos expression increased in somatostatin- and GHRH-immunoreactive cells at the time of the estradiol-induced LH surge in intact anestrous ewes. Estradiol significantly (P < 0.05) increased the percentage of GHRH (estradiol, 75% +/- 3%; no estradiol, 19% +/- 2%) neurons expressing c-fos in the hypothalamus. The percentage of somatostatin-immunoreactive neurons coexpressing c-fos in the estradiol-treated animals was significantly (P < 0.05) higher (periventricular, 44% +/- 3%; arcuate, 72% +/- 5%; VMN, 81% +/- 5%) than in the control animals (periventricular, 22% +/- 1%; arcuate, 29% +/- 3%; VMN, 31% +/- 3%). The present study suggests that estradiol modulates the activity of GHRH and somatostatin neurons but that this effect is most likely mediated through an indirect interneuronal pathway.
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PMID:Somatostatin-14 neurons in the ovine hypothalamus: colocalization with estrogen receptor alpha and somatostatin-28(1-12) immunoreactivity, and activation in response to estradiol. 1277 14

Enterochromaffin-like (ECL) cell hyperplasia and then irreversible neoplasia can be generated in the African rodent Mastomys natalensis using the H2 receptor blocker, loxtidine, for 8-16 wk. We used a GeneChip approach complemented by standard technologies to identify gene expression alterations in the gastric mucosa during gastrin-mediated ECL cell transformation. Gastric mucosa (mucosal scrapping) and ECL cell-enriched fractions were obtained from untreated Mastomys (controls) and from animals treated with loxtidine for 8 wk (hyperplasia). Tumor ECL cells were obtained by hand-dissection of gastric ECL cell nodules from animals treated with loxtidine for >16 wk and from a spontaneously developed ECL cell tumor. RNA was isolated, examined on rat U34A GeneChips, and comparison analysis was performed to identify altered gene expression. Alterations in gene expressions were examined further by immunohistochemistry, quantitative RT-PCR (Q-RT-PCR), sequencing and Western blot. GeneSpring analysis demonstrated alterations in few genes (<20) in hyperplastic and tumor mucosa. The histamine H1 receptor was consistently increased in proliferating mucosa. This gene change was confirmed by Q-RT-PCR. Other genes showing alterations included neural-(chromogranin A and somatostatin), cell-cycle-, and AP-1-associated genes. Immunostaining confirmed alterations in neural markers. Cluster analysis of ECL cell-enriched samples demonstrated that c-fos and junD were differently regulated. Q-RT-PCR and Western blot in prospectively collected gastric mucosal samples confirmed the differential expression of Fos and Jun. The negative regulators of AP-1, JunD, and Menin were decreased in tumor mucosa. A missense of unknown function was noted in the menin gene. Hypergastrinemia in an animal model of gastric carcinoids differentially altered the histamine type 1 receptor and gene expression and protein composition of AP-1. These results suggest that expression of this receptor and an altered composition of AP-1 with a loss of inhibition play a role in ECL cell transformation.
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PMID:Global expression analysis of ECL cells in Mastomys natalensis gastric mucosa identifies alterations in the AP-1 pathway induced by gastrin-mediated transformation. 1560 48

This article intends to show how the cerebellum, a structure ordinarily not considered in mediating breathing or cardiovascular control, may play a critical role in compensatory responses particularly to hypoxic insults occurring pre and/or postnatally and thus may be involved in the sudden unexplained perinatal and infant death. Besides the ontogenesis of the cerebellar cortex in man, we reported alterations of biopathological features (neuronal immaturity, altered apoptotic programs, negative expression of somatostatin and EN2 gene, intense c-fos expression positivity, astrogliosis) in the cortex and in the dentate nucleus of the 63% of sudden deaths, and only in 10% of the controls. The correlation of these results with the mother's smoking habit was highly significant. Therefore, we support the hypothesis, already expressed in previous studies on brainstem, of a close relation between maternal cigarette smoking and a wide range of morpho-physiological defects of the brain, leading to unexplained sudden death in stillbirths, newborns, and Sudden Infant Death Syndrome (SIDS) victims.
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PMID:Alterations of biological features of the cerebellum in sudden perinatal and infant death. 1690 Jun 66

The aims of this study were to investigate in the human cerebellar cortex the structural and biological ontogenetic features, the possible presence of alterations in cases of sudden unexplained fetal and infant death, and the involvement of the maternal cigarette smoking in developmental abnormalities. We analyzed 52 brains of fetal and infant death victims, aged from the second gestational trimester to 12th postnatal month. In the cerebellar cortex we evaluated, besides the morphological aspects, the expression of several biomarkers implicated in proliferative processes (c-fos, proliferating cell nuclear antigen, and apoptosis) as well as the presence of the neurotransmitter somatostatin, which is strongly implicated in central nervous system differentiation, and of EN2 gene. The observed features of the cerebellar cortex, mainly confined to the transient external granular layer, were high proliferative activity and high expression of both somatostatin and EN2 gene in prenatal life and high apoptotic index after birth. In 41% of the sudden unexplained death victims, in the greater part with smoking mothers, we observed different biopathological alterations of the cerebellar cortex. Maternal smoking is increasingly being demonstrated to be one of the main contributors to developmental neurological alterations in the offspring.
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PMID:Ontogenesis of human cerebellar cortex and biopathological characterization in sudden unexplained fetal and infant death. 1733 3

The neuroendocrine 44-2C cells synthesize, secrete, and manifest differential regulation of calcitonin (CT), CT gene-related peptide (CGRP), neurotensin (NT), and somatostatin (SS). These cells maintain differentiated function when grown in serum-free, growth factor and hormone-deprived milieu. The cells continue to secrete CT, CGRP, NT, and SS and differentially respond to cellular secretagogues. In serum-free cultures, the cells produce biologically active acidic fibroblast growth factor (aFGF) and differentially regulate the expression of the protooncogene fos (c-fos).
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PMID:44-2C cells a neuroendocrine model to study neuropeptide, oncogene, and growth factor gene regulation. 1841 Nov 1

The En2 gene, coding for the homeobox-containing transcription factor Engrailed-2 (EN2), has been associated to autism spectrum disorder (ASD). Due to neuroanatomical and behavioral abnormalities, which partly resemble those observed in ASD patients, En2 knockout (En2(-/-)) mice have been proposed as a model for ASD. In the mouse embryo, En2 is involved in the specification of midbrain/hindbrain regions, being predominantly expressed in the developing cerebellum and ventral midbrain, and its expression is maintained in these structures until adulthood. Here we show that in the adult mouse brain, En2 mRNA is expressed also in the hippocampus and cerebral cortex. Hippocampal En2 mRNA content decreased after seizures induced by kainic acid (KA). This suggests that En2 might also influence the functioning of forebrain areas during adulthood and in response to seizures. Indeed, a reduced expression of parvalbumin and somatostatin was detected in the hippocampus of En2(-/-) mice as compared to wild-type (WT) mice, indicating an altered GABAergic innervation of limbic circuits in En2(-/-) mice. In keeping with these results, En2(-/-) mice displayed an increased susceptibility to KA-induced seizures. KA (20 mg/kg) determined more severe and prolonged generalized seizures in En2(-/-) mice, when compared to WT animals. Seizures were accompanied by a widespread c-fos and c-jun mRNA induction in the brain of En2(-/-) but not WT mice. Long-term histopathological changes (CA1 cell loss, upregulation of neuropeptide Y) also occurred in the hippocampus of KA-treated En2(-/-) but not WT mice. These findings suggest that En2(-/-) mice might be used as a novel tool to study the link between epilepsy and ASD.
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PMID:Increased susceptibility to kainic acid-induced seizures in Engrailed-2 knockout mice. 1918 8

Mutations in doublecortin (DCX) are associated with intractable epilepsy in humans, due to a severe disorganization of the neocortex and hippocampus known as classical lissencephaly. However, the basis of the epilepsy in lissencephaly remains unclear. To address potential functional redundancy with murin Dcx, we targeted one of the closest homologues, doublecortin-like kinase 2 (Dclk2). Here, we report that Dcx; Dclk2-null mice display frequent spontaneous seizures that originate in the hippocampus, with most animals dying in the first few months of life. Elevated hippocampal expression of c-fos and loss of somatostatin-positive interneurons were identified, both known to correlate with epilepsy. Dcx and Dclk2 are coexpressed in developing hippocampus, and, in their absence, there is dosage-dependent disrupted hippocampal lamination associated with a cell-autonomous simplification of pyramidal dendritic arborizations leading to reduced inhibitory synaptic tone. These data suggest that hippocampal dysmaturation and insufficient receptive field for inhibitory input may underlie the epilepsy in lissencephaly, and suggest potential therapeutic strategies for controlling epilepsy in these patients.
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PMID:Mice lacking doublecortin and doublecortin-like kinase 2 display altered hippocampal neuronal maturation and spontaneous seizures. 1934 86

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