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)

Using RT and amplification, we have detected specific RNA transcripts encoding somatostatin in FRTL-5 thyroid cells. This observation indicates that within the thyroid context, expression of somatostatin is not restricted to the parafollicular C cells. Transfection of FRTL-5 cells with constructs containing either the complete somatostatin gene promoter or deletions carrying the cAMP response element-binding site allowed us to demonstrate that transcription of the somatostatin gene is hormonally regulated by TSH. Blockage of somatostatin by specific antibodies resulted in an increased capacity of TSH-induced FRTL-5 cell-conditioned medium to promote cell proliferation, demonstrating that under physiological conditions, somatostatin exerts a cytostatic effect on FRTL-5 cells growth. Somatostatin treatment of FRTL-5 cells resulted in a growth retardation, caused by a dose-response delay in the G1 phase of the cell cycle. This effect appears to be mediated by the cyclin-dependent kinase inhibitor p27kip1, which is clearly down-regulated in FRTL-5 cells treated with TSH and whose expression is reestablished by somatostatin in a dose-dependent manner. Participation of somatostatin in the control of FRTL-5 cell proliferation is in agreement with the detection of specific somatostatin receptor type 2. Flow cytometric assays reveal that FRTL-5 cells transformed with the K-ras oncogene are still sensitive to somatostatin treatment, whereas fully neoplastic FRT cells no longer respond to this peptide. Taking together, the results demonstrate the participation of an autocrine loop in the control of thyroid cell proliferation, and the possibility that this mechanism could be altered in the process of thyroid carcinogenesis.
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PMID:Somatostatin is expressed in FRTL-5 thyroid cells and prevents thyrotropin-mediated down-regulation of the cyclin-dependent kinase inhibitor p27kip1. 988 11

We have identified cotton rats with a high female-predominant occurrence of spontaneous gastric carcinomas localized to the oxyntic mucosa, classified as malignant enterochromaffin-like (ECL) omas. The present study was made to further characterize these ECLomas and surrounding oxyntic mucosa, both morphologically using histochemical and immunohistochemical methods, and for gene expression by northern blot analysis. Among eight female cotton rats, three had an irregularly thickened oxyntic mucosa, increased stomach weight and a high serum gastrin level. Histopathological examination showed adenomatous hyperplasia of the thickened oxyntic mucosa with areas of an invasive neoplastic tumour. Immunohistochemistry, using the general neuroendocrine cell marker chromogranin A (CgA) and the specific ECL cell marker histidine decarboxylase (HDC), showed a considerably increased ECL cell density. These ECL cells displayed active proliferation, with hyperplasia, dysplasia and neoplasia. Parietal cells were not found in the tumour tissue. Parietal cell density was only slightly reduced in the surrounding oxyntic mucosa. The antral mucosa was histopathologically normal with a normal number of gastrin-immunoreactive cells. Likewise, somatostatin-immunoreactive cells did not show any differences in the antral and oxyntic mucosa between rats with pathological and normal oxyntic mucosa. Northern blot analysis revealed increased expression of CgA and HDC mRNA in the thickened oxyntic mucosa, whereas H(+)/K(+) ATPase mRNA was similar in the oxyntic mucosa of those with thickened and normal oxyntic mucosa. Gastrin mRNA in the antral mucosa was high in animals with thickened oxyntic mucosa. Somatostatin mRNA expression was similar in the antral mucosa of control animals and animals with a thickened oxyntic mucosa. We conclude that the spontaneous gastric carcinoma occurring in female cotton rats is an ECLoma developing secondary to hypergastrinaemia due to reduced intragastric pH. The mechanism for reduced acidity is not known, but is not gastric atrophy.
Carcinogenesis 2000 Jan
PMID:Spontaneous ECLomas in cotton rats (Sigmodon hispidus): tumours occurring in hypoacidic/hypergastrinaemic animals with normal parietal cells. 1060 29

Gastrin is a hormone regulating gastric acid secretion and the growth of the gastrointestinal epithelium. It is expressed by endocrine tumors and by adenocarcinomas of the gastroenteropancreatic region and may represent an autocrine tumor growth factor. Gastrin is also implicated in the genesis of peptic ulcer disease both in conjunction with H. pylori infections and with gastrin-producing tumors. The secretion and expression of gastrin are under the paracrine control of somatostatin, produced by D cells situated in close contact with gastrin-producing G cells. D cells also contain neuronal nitric oxide synthase and appear to regulate apoptosis of G cells by paracrine release of nitric oxide. Both G and D cells are derived from a common multihormonal precursor cell present in the regenerative (isthmus) region of the gastric units. The precursor cells have been suggested to undergo asymmetrical divisions resulting in gastrin- and somatostatin-producing daughter cells that remain in paracrine contact during their migration into the glands. The precursor cells also give rise to the third main antropyloric endocrine cell type; the serotonin-producing EC cell. The maturation of all of these cell types is regulated by a number of transcription factors containing homeobox motifs (Pdx-1, Pax 4 and 6, Isl-1, Nkx6.1). Many of these also regulate the development of the central nervous system and the pancreas. The use of different combinations of these factors for regulating the expression of different hormones may explain the phenomenon of abberant hormone expression during development and carcinogenesis and the occurrence of multihormonal cells.
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PMID:Developmental biology of gastrin and somatostatin cells in the antropyloric mucosa of the stomach. 1070 44

Somatostatin (SRIF) is a potent antiproliferative signal for both normal and tumoral mammalian cells and an alteration in the SRIF receptor expression pattern has been associated with carcinogenesis. In the present study, the relevance of SRIF signaling to human male germ cell tumors was assessed at the receptor level. The expression of five SRIF receptor (sst1-sst5) mRNAs was estimated by RT-PCR and compared between normal and tumoral testes. All 12 normal testicular tissues studied contained sst3 and sst5 receptor transcripts whereas sst4 was present in almost all (11 of 12). sst1 transcripts were consistently absent while the majority (11/12) of normal samples studied did not contain sst2 mRNA. Parallel assessment of SRIF receptor mRNAs in 10 seminoma testicular germ cell tumors showed expression of a single receptor type, sst5, in all samples analyzed. All seminoma samples were depleted in transcripts corresponding to sst1 and sst2 receptors while either sst3 or sst4 mRNAs were absent in almost all (9 of 10) tumoral samples studied. The comparison of SRIF receptor expression between normal tissue and seminoma tumors thus points to a selective loss of sst3 and sst4 mRNA expression in seminomas. Altogether these data indicate that: (i) normal human testes are putative SRIF targets; (ii) loss of sst3 and sst4 SRIF receptor expression might be associated with seminoma carcinogenesis.
Carcinogenesis 2000 Apr
PMID:Evidence for a selective loss of somatostatin receptor subtype expression in male germ cell tumors of seminoma type. 1075 19

The modifying effects of octreotide acetate, a somatostatin (SMS) analogue shown to inhibit secretion of digestive enzymes, bicarbonate and pancreatic juice, on the initiation phase of pancreatic carcinogenesis were investigated in hamsters simultaneously treated with N-nitrosobis(2-oxopropyl)amine (BOP). Groups 1-3, each consisting of 20 animals, were given BOP subcutaneously once a week three times at a dose of 10 mg/kg body weight during administration of octreotide acetate for 28 days via osmotic pumps implanted subcutaneously at doses of 6 microg/day (group 1), 3 microg/day (group 2) or 0 microg/day (saline) (group 3). Group 4-6 animals (each group ten animals) were similarly administered octreotide acetate for the same period with five subcutaneous injections of saline. At the termination of experimental week 40, the incidences and multiplicities of pancreatic ductal adenocarcinomas and dysplastic lesions did not significantly differ among groups 1-3. No neoplastic lesions were found in groups 4-6. Subcutaneous administration of octreotide acetate resulted in obviously increased plasma octreotide levels. Our results thus suggest that this SMS analogue may not modulate the initiation of BOP-induced pancreatic carcinogenesis, regardless of its pharmacological action.
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PMID:Effects of octreotide, a somatostatin analogue, on initiation of pancreatic carcinogenesis in hamsters with N-nitrosobis(2-oxopropyl)amine. 1097 4

Colonic carcinoma was induced in male Sprague-Dawley rats by injecting them with 1,2-dimethylhydrazine dihydrochloride. Control rats were injected with EDTA solution. Tissue specimens of colon from four groups of animals: (i) rats without tumour, (ii) with dysplasia and lymphoid hyperplasia, (iii) with colonic adenocarcinoma, and (iv) controls, were investigated. The colonic endocrine cells were detected by immunocytochemistry and quantified by computerised image analysis. Peptide YY (PYY)- and serotonin-immunoreactive cells were found in the colon of all the groups investigated. There were few somatostatin- or enteroglucagon-immunoreactive cells and no pancreatic polypeptide (PP)-immunoreactive cells in the colon of any of the groups studied. The density of PYY-immunoreactive cells increased significantly in rats with dysplasia and lymphoid hyperplasia and in rats with colon carcinoma. There was no statistically significant difference as regards cell secretory index (CSI) or nuclear area of PYY-immunoreactive cells in any of treated groups examined. Nor was there any statistically significant difference between all treated animal groups and controls, as regards cell density, CSI, or nuclear area of serotonin-immunoreactive cells. The present observations in an animal model of human colon carcinoma support the assumption that neuroendocrine peptides in the gut are involved in the carcinogenesis of colorectal carcinoma. However, The nature of the changes in the colonic endocrine cells observed here differed from those in patients with colon carcinoma, possibly due to a difference between the response of young rats to an induced colon carcinoma and a spontaneously developed carcinoma in elderly humans, or due to a species difference.
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PMID:Colonic endocrine cells in rats with chemically induced colon carcinoma. 1151 Sep 74

Gastric Helicobacter pylori (Hp) infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis resulting from the long-term Hp infection but functional aspects accompanying this Hp-induced progression from gastritis to the cancer, especially changes in gastric acid secretion, gastric blood flow (GBF) and gastrin-somatostatin link have been little studied. It is unclear whether Hp eradication therapy alters the functional and the histopathological changes in this animal model of Hp-infection. We examined the effects of intragastric (i.g.) inoculation of Mongolian gerbils with Hp strain (cagA+ vacA+, 5 x 10(6) CFU/ml) that had been isolated from a patient with gastric ulcer as compared to those induced by vehicle (saline) in gerbils with or without gastric fistula (GF) at 1.2, 4, 6, 9, 12 and 30 wks upon gastric inoculation with this bacteria. An attempt was made to evaluate the influence of anti-Hp triple therapy with omeprazole, amoxicillin and tinidazol on gastric Hp-infection and Hp-induced functional impairment of the gastric mucosa. Gastric mucosal biopsy specimens were taken for the assessment of the morphological changes and the presence of Hp infection using rapid urease test (CLO-test) and the density of Hp-colonization were assessed by counting of the number of bacterial colonies per plate. Gastric blood flow (GBF) was measured by H2-gas clearance technique and the venous blood and the gastric content were collected for the measurement of plasma gastrin levels and the gastric luminal somatostatin level by radioimmunoassay (RIA). The Hp in gastric mucosa was detected in all animals by culture and rapid urease test at various periods upon Hp inoculation. Basal gastric acid in non-infected conscious gerbils with GF reached the level of about 28 +/- 4 micromol/h and this was reduced by over 50% immediately upon the Hp-inoculation and persisted for time intervals tested up to 30 wk. Early lesions were seen 4 wks after the Hp-inoculation and consisted of chronic gastritis with thickened gastric mucosal foldings and elongated interfoveolar ridges. Edema and congestion as well as significant mucosal inflammatory infiltration with lymphoid infiltrate in lamina propria of the mucosa occurred in all infected gerbils. Adenomatous hyperplasia with cellular atypia was observed at 12 wk upon Hp-inoculation together with increased mitotic activity and numerous apoptotic bodies formation, while lamina propria was reduced leaving dilated atypical gastric gland situated "back-to-back". This glandular atypia failed to show lamina propria or submucosa infiltration corresponding to gastric intraepithelial neoplasia. The GBF in Hp-infected gerbils was significantly lower, and a 6-7 fold increase in plasma gastrin levels combined with a significant fall in gastric luminal somatostatin contents observed at all tested periods as compared to vehicle-controls and these effects were counteracted by anti-Hp triple therapy. We conclude that: 1). Hp-infection in Mongolian gerbils in early stages before adenocarcinoma formation results in the development of typical functional and pathological changes such as suppression of gastric secretion and impairment of both, gastric mucosal microcirculation and gastrin-somatostatin link, and 2). this deleterious influence of Hp on gastric morphology and gastric functions is greatly attenuated in gerbils treated with Hp-eradication therapy.
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PMID:Triple eradication therapy counteracts functional impairment associated with Helicobacter pylori infection in Mongolian gerbils. 1267 17

Somatostatin is a potent antiproliferative signal in both tumoral and normal mammalian cells, and altered somatostatin receptor (sst) expression is associated with carcinogenesis in human tissues. In this study, two normal and three tumoral human pineal glands were analyzed using the reverse transcriptase-polymerase chain reaction (RT-PCR) for the presence of mRNA coding for the five different somatostatin receptors (sst1-sst5). Pineal parenchymal tumor (PPT) differentiation was confirmed by immunohistochemical detection of neuroendocrine markers (synaptophysin, neurofilaments, and chromogranin A). The presence of mRNA coding for c-myc, a proto-oncogene, and for tryptophan hydroxylase (TPOH), serotonin N-acetyltransferase (NAT), and hydroxyindole-O-methyltransferase (HIOMT), enzymes of the melatonin pathway, was also analyzed by RT-PCR. Only the tumoral tissues contained c-myc mRNA. All five tissues contained TPOH, NAT, and HIOMT mRNA, the levels of HIOMT mRNA being lower in PPT than in the normal pineal gland, suggesting that PPT retain the ability to synthesize melatonin. All tissues contained sst1, sst2, and sst3 transcripts, but not sst4, while small amounts of sst5 mRNA were only found in normal pineal glands. Real-time PCR, performed only with the most abundant subtpe sst2, evidenced an about sixfold higher level in in normal pineal glands. These results demonstrate the presence of somatostatin receptors in the human pineal gland, as described in other species, and point to a differential expression of the sst2 and sst5 subtypes associated with carcinogenesis.
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PMID:Differential somatostatin receptor subtype expression in human normal pineal gland and pineal parenchymal tumors. 1270 86

The molecular basis of testicular germ cell tumourigenesis are not well elucidated. Growth factors regulate cell growth, differentiation and apoptosis. Major families of growth factors are present in the male gonad from early fetal development to adult life. They are involved in germ cell proliferation and differentiation. Growth signalling pathways suffer deregulation in many human malignancies. Given the importance of growth signals in normal testicular development and their acquired deregulation in most human cancers, growth factors and signalling molecules that have been implicated in the genesis of testicular germ cell tumours, are reviewed. We detected a somatic mutation of SMAD4 gene, responsible for loss of protein function in seminomas. This mutational inactivation may affect the activity of several members of TGFbeta superfamily (TGFbeta, activin, inhibin, BMP). VEGF expression has been shown to predict metastasis in seminomas. A significant association of HST-1 expression, a member of fibroblast growth factors, with the nonseminomatous phenotype and with tumour stage has been described. In contrast, C-KIT is expressed by seminomas only, from the preinvasive stage. Despite intense expression in almost all seminomas, activating mutation of C-KIT gene is seldom reported. Recently, the first animal model of classical testicular seminoma has been identified in transgenic mouse overexpressing GDNF. RET (GDNF receptor) expression is demonstrated in human seminomas, and not in nonseminomatous tumours. However, the exact molecular alterations of GDNF/RET/GFRalpha1 complex in germ cell tumours are not known. Finally, beside growth factors, other signalling molecules such as peptide hormones may be involved in testicular carcinogenesis. We have demonstrated a specific pattern of somatostatin receptors expression in each type of testicular germ cell tumours, with a loss of sst3 and sst4 in seminomas and loss of sst4 and expression of sst1 in nonseminomas only. These data suggest an antiproliferative action of somatostatin in testicular cancers. In summary, many growth factors and signalling molecules seem to represent specific markers for different histological types of germ cell tumours (seminomas versus nonseminomas) and may play a role in the differentiation of germ cell tumours. Despite a complex signalling pathway involved in the physiological functions of male gonad, little is known about the implication of this signalling network in testicular malignancies. From a practical stand-point, further studies on the role of growth factors in human germ cell tumours may offer a new therapeutical perspective with the development of specific pharmacological signalling modulators that could be used as therapeutic agents.
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PMID:Growth regulatory factors and signalling proteins in testicular germ cell tumours. 1275 64

Rat stomach carcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are widely used as a model for differentiated-type human stomach carcinomas. Here, we analyzed expression profiles in five MNNG-induced rat stomach carcinomas by the high-density oligonucleotide microarray containing approximately 8000 probe sets. 244 and 208 genes were up- and down-regulated, respectively, by 3-fold and over in four or five carcinomas. Up-regulated genes included those involved in the extracellular matrix remodeling (i.e. Collagen types I, III, V, MMP3), immune response (i.e. lysozyme, complements) and in ossification (i.e. Osteoblast-specific factor). Genes down-regulated included those related to hydrocarbon metabolism (i.e. aldose A, aldehyde dehydrogenase), gastric juice (ion transporter genes) and mucous production (Mucin 5) and gastric hormones (gastrin and somatostatin). The expression profile of the MNNG-induced rat stomach carcinomas shared many features with human stomach carcinomas while cyclin D1 was down-regulated in rat stomach carcinomas but up-regulated in human stomach carcinomas. When the expression profile of the MNNG-induced rat stomach carcinomas was compared with those of two kinds of rat mammary carcinomas, only 13 genes were commonly altered. These results showed that MNNG-induced stomach carcinomas possessed infiltrating capacity and had lost differentiated phenotypes of the stomach, in the same way as human stomach carcinomas, and could be used as a good model for them from the viewpoint of molecular expression profile.
Carcinogenesis 2003 May
PMID:Global expression analysis of N-methyl-N'-nitro-N-nitrosoguanidine-induced rat stomach carcinomas using oligonucleotide microarrays. 1277 Oct 29


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