Clinical and histopathological tumour progression in ECL cell carcinoids (“ECLomas”)

Qvigstad, Gunnar; Falkmer, Sture; Westre, Bjørn; Waldum, Helge L.

doi:10.1111/j.1699-0463.1999.tb01513.x

Cited by 65 publications

(64 citation statements)

References 29 publications

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“…A proportion of the tumor cells was also positive for these markers. During follow-up of a patient with an ECL cell carcinoid, a gradual reduction in the number of CgA-and SM-positive cells was observed, which indicates a dedifferentiation of ECL cells over time (24). Such dedifferentiation could also explain why not all cells are CgA/HDC/SM positive in areas with high proliferation or cancer in loxtidine-dosed cotton rats.…”

Section: Discussionmentioning

confidence: 97%

ECL-Cell Derived Gastric Cancer in Male Cotton Rats Dosed with the H2-Blocker Loxtidine

et al. 2004

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Spontaneously hypergastrinemic cotton rats (Sigmodon hispidus) develop tumors that have the phenotype of an adenocarcinoma but most likely originate from the enterochromaffin-like (ECL) cells. Among inbred animals ϳ50% of the females, but <1% of males develop spontaneous gastric carcinomas. Gastrin is the principle carcinogen in this model, as >4 months of hypergastrinemia results in carcinoma, but a gastrin receptor antagonist prevents carcinomas. Carcinomas can also be induced by partial corpectomy. In the present study, the insurmountable H2-receptor antagonist loxtidine (200 mg/kg/day) was given to male cotton rats for 6 months. The loxtidine-dosed animals developed hypergastrinemia, whereas control animals remained normogastrinemic. At termination, 4 of 5 cotton rats had cancer located to the oxyntic mucosa, whereas 1 animal had dysplasia. The gastric mucosa of all of the control animals was normal. In the dysplastic mucosa of loxtidine-dosed animals there was a marked increase in chromogranin A-positive cells, where numerous groups of cells also stained positive with the Sevier-Munger technique. In areas of high proliferation and cancer there were also histidine decarboxylase, chromogranin A, and Sevier-Munger-positive cells, altogether indicating an ECL cell origin of the tumors. This represents an interesting animal model where ECL cell-derived gastric cancer can be induced by pharmacological acid inhibition in 6 months.

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Section: Discussionmentioning

confidence: 97%

ECL-Cell Derived Gastric Cancer in Male Cotton Rats Dosed with the H2-Blocker Loxtidine

et al. 2004

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“…Sections, about 4 -5 micron thick, were employed for the IHC examinations, using the Vectastain ABC kit (Vector Lab., Burlingame, CA, USA), and/or Tyramide signal amplification technique (NEN LifeScience Products, Boston, MA, USA), as previously described (Qvigstad et al, 1999). Chromogranin A antiserum (1 : 500) was provided by Incstar (Stillwater, MN, USA), monoclonal mouse antisynaptophysin antiserum (1 : 20) by Dako (Glostrup, Denmark), anti rat neuron-specific enolase (1 : 500) by Polysciences (Warrington, PA, USA), and antineurofilament M (1 : 4000) by Fitzgerald (MA, USA).…”

Section: Immunohistochemical and Ultrastructural Examinationsmentioning

confidence: 99%

Identification of novel neuroendocrine-specific tumour genes

et al. 2008

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Neuroendocrine tumours (NETs) comprise a heterogenous group of malignancies with an often unpredictable course, and with limited treatment options. Thus, new diagnostic, prognostic, and therapeutic markers are needed. To shed new lights into the biology of NETs, we have by cDNA transcript profiling, sought to identify genes that are either up-or downregulated in NE as compared with non-NE tumour cells. A panel of six NET and four non-NET cell lines were examined, and out of 12 743 genes examined, we studied in detail the 200 most significantly differentially expressed genes in the comparison. In addition to potential new diagnostic markers (NEFM, CLDN4, PEROX2), the results point to genes that may be involved in the tumorigenesis (BEX1, TMEPAI, FOSL1, RAB32), and in the processes of invasion, progression and metastasis (MME, STAT3, DCBLD2) of NETs. Verification by real time qRT -PCR showed a high degree of consistency to the microarray results. Furthermore, the protein expression of some of the genes were examined. The results of our study has opened a window to new areas of research, by uncovering new candidate genes and proteins to be further investigated in the search for new prognostic, predictive, and therapeutic markers in NETs.

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“…This receptor has been shown to be coexpressed with gastrin in several GI tumor cell lines (53) and in human gastric carcinoids (38), indicating the existence of an autocrine growth stimulatory loop. The malignant potential of carcinoids is associated with hypergastrinemia (24). These studies suggest that gastrin plays an important role in neuroendocrine tumor biology.…”

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confidence: 91%

Inducible cAMP early repressor suppresses gastrin-mediated activation of cyclin D1 and c-fosgene expression

Steigedal¹,

Bruland²,

Misund³

et al. 2007

American Journal of Physiology-Gastrointestinal and Liver Physi

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Steigedal TS, Bruland T, Misund K, Thommesen L, Laegreid A. Inducible cAMP early repressor suppresses gastrin-mediated activation of cyclin D1 and c-fos gene expression. Am J Physiol Gastrointest Liver Physiol 292: G1062-G1069, 2007. First published December 21, 2006; doi:10.1152/ajpgi.00287.2006.-The gastric hormone gastrin and its precursors promote proliferation in several gastrointestinal cell types. Here we show that gastrin induces transcription of cell cycle gene cyclin D1 and protooncogene c-fos in the neuroendocrine pancreatic cell line AR42J and that this gastrin response is inhibited by endogenous inducible cAMP early repressor (ICER). The transcriptional repressor ICER is known to downregulate both its own expression and the expression of other genes containing cAMPresponsive elements (CREs). Using siRNA, we also show that CRE promoter elements are the targets of endogenous ICER in AR42J cells as well as in the neuroendocrine cell line RIN5F. Our results suggest that ICER plays an important role in molecular mechanisms governing gastrin-mediated growth by modulating gastrin's transcriptional activation of growth-related genes. Our finding that ICER modulates pituitary adenylate cyclase-activating polypeptide-activated gene expression also indicates a regulatory effect of ICER in the responses of neuroendocrine cells to peptides other than gastrin.neuroendocrine gene regulation; gastrointestinal proliferation; gastrin THE PEPTIDE HORMONE GASTRIN is well characterized as a stimulant of gastric acid secretion by stimulation of enterochromaffin-like (ECL) cells to produce histamine, which in turn stimulates the parietal cells in the oxyntic mucosa to release HCl (36,48). Gastrin is an important growth factor for the fetal pancreas (50) and a potent stimulant for the growth of gastric mucosa (4,5,46). Transgenic mice overexpressing gastrin exhibit increased proliferation of the oxyntic mucosa (51), whereas gastrin-deficient mice develop abnormal gastrointestinal (GI) mucosa with immature cells (7,12). In addition, there is abundant evidence to suggest that gastrin may play an important role in tumor biology, as gastrin is shown to regulate tumor cell growth (4, 5) and stimulate tumor cell invasion (4, 5, 13). Hypergastrinemia is associated with the occurrence of gastric ECL cell carcinoid tumors (4,5,28,46) and with an increased risk of gastric and colorectal carcinoma (5), indicating a role in carcinogenesis. The biological actions of gastrin are exerted through binding to the gastrin/cholecystokinin (CCK2) receptor. This receptor has been shown to be coexpressed with gastrin in several GI tumor cell lines (53) and in human gastric carcinoids (38), indicating the existence of an autocrine growth stimulatory loop. The malignant potential of carcinoids is associated with hypergastrinemia (24). These studies suggest that gastrin plays an important role in neuroendocrine tumor biology.Inducible cAMP early repressor (ICER) is a transcriptional repressor encoded by the cAMP-responsive element (CRE) modulatin...

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Clinical and histopathological tumour progression in ECL cell carcinoids (“ECLomas”)

Cited by 65 publications

References 29 publications

ECL-Cell Derived Gastric Cancer in Male Cotton Rats Dosed with the H2-Blocker Loxtidine

ECL-Cell Derived Gastric Cancer in Male Cotton Rats Dosed with the H2-Blocker Loxtidine

Identification of novel neuroendocrine-specific tumour genes

Inducible cAMP early repressor suppresses gastrin-mediated activation of cyclin D1 and c-fosgene expression

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