Expression of the Protooncogene jun Is Induced in the Rat Pancreas by Cerulein Infusion

Ferrara, C.; Gress, T; Müeller-Pillasch, Friederike; Lutz, Manfred P.; Weidenbach, H; Poletti, Anna; Lerch, Markus M.; Favero, G. Del; Adler, Guido

doi:10.1097/00006676-199708000-00008

Cited by 4 publications

(3 citation statements)

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“…AP-1 activation in the pancreas has not been described previously. So far, two studies reported pancreatic induction of the protoncogenes c-fos and c-jun during ceruleininduced pancreatitis in mice (13) and rats (10). The role of the different AP-1 subunits we found activated in taurocholate pancreatitis in the expression of genes mediating the inflammatory response remains to be determined.…”

Section: Discussionmentioning

confidence: 75%

Localized pancreatic NF-κB activation and inflammatory response in taurocholate-induced pancreatitis

Vaquero

Gukovsky

Zaninovic

et al. 2001

American Journal of Physiology-Gastrointestinal and Liver Physi

144

107

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Transcription factor nuclear factor-kappaB (NF-kappaB) is activated in cerulein pancreatitis and mediates cytokine expression. The role of transcription factor activation in other models of pancreatitis has not been established. Here we report upregulation of NF-kappaB and inflammatory molecules, and their correlation with local pancreatic injury, in a model of severe pancreatitis. Rats received intraductal infusion of taurocholate or saline, and the pancreatic head and tail were analyzed separately. NF-kappaB and activator protein-1 (AP-1) activation were assessed by gel shift assay, and mRNA expression of interleukin-6, tumor necrosis factor-alpha, KC, monocyte chemoattractant protein-1, and inducible nitric oxide synthase was assessed by semiquantitative RT-PCR. Morphological damage and trypsin activation were much greater in the pancreatic head than tail, in parallel with a stronger activation of NF-kappaB and cytokine mRNA. Saline infusion mildly affected these parameters. AP-1 was strongly activated in both pancreatic segments after either taurocholate or saline infusion. NF-kappaB inhibition with N-acetylcysteine ameliorated the local inflammatory response. Correlation between localized NF-kappaB activation, cytokine upregulation, and tissue damage suggests a key role for NF-kappaB in the development of the inflammatory response of acute pancreatitis.

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Section: Discussionmentioning

confidence: 75%

Localized pancreatic NF-κB activation and inflammatory response in taurocholate-induced pancreatitis

Vaquero

Gukovsky

Zaninovic

et al. 2001

American Journal of Physiology-Gastrointestinal and Liver Physi

144

107

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“…Auf humanen hepatozellulären Karzinomen wurden weder CCK-A-, noch CCK-B/Gastrin-Rezeptoren gefunden [88]. Beim Pankreaskarzinom ist die Stimulation des CCK-Rezeptors mit einer verstärkten Expression des Proto-Onkogens c-jun verbunden, das als Teil des AP-1-Transskriptionsregulationskomplexes wirken kann [89,90]. Dem AP-1-Komplex wird dabei eine entscheidende Bedeutung für die Proliferationsinitiierung zugeschrieben.…”

Section: Cholezystokinin (Cck)unclassified

Die Bedeutung von Peptidhormonen des Magen-Darm-Trakts für das Wachstum von humanen gastrointestinalen Tumoren*

Lersch¹,

Erdmann²,

Schusdziarra³

2001

TumorDiagnostik & Therapie

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Zusammenfassung. Rezeptoren für Peptidhormone wurden auf Tumoren und Tumorzelllinien des Gastrointestinaltrakts nachgewiesen. In der Übersicht werden Daten über Peptide, für deren Agonisten bzw. Antagonisten Wirkungen bei humanen Tumoren gezeigt wurden, zusammenfassend dargestellt. Gastrin-Antagonisten können das Wachstum von Pankreas-und Kolonkarzinomzelllinien in vitro und in Nacktmäusen hemmen, nicht dagegen bisher bei Patienten mit Pankreas-und Magenkarzinomen. Eine Rolle des Gastrins bei der Karzinogenese des Magen-und Kolonkarzinoms wird diskutiert. Weder Cholezystokinin-Antagonisten noch -agonisten konnten das Wachstum von Pankreaskarzinomen bei Patienten hemmen. Über Neurotensin-Rezeptoren kann in vitro das Wachstum von Kolon-und Pankreaszelllinien gesteigert werden. Vasoaktives Intestinales Peptid (VIP) beeinflusst das Wachstum von humanen gastrointestinalen Tumoren unterschiedlich. Das Peptid YY kann das Wachstum humaner Pankreas-und Kolonkarzinomzelllinien hemmen. Der Einsatz von Somatostatin und Analoga bei neuronendokrinen Tumoren ist etabliert. Auch bei Kolonkarzinomen und deren Vorläufern sowie beim hepatozellulären Karzinom könnten diese Substanzen wirksam sein.Schlüsselwörter: Gastrointestinale Peptidhormone ± Agonisten ± Antagonisten ± Gastrointestinale Tumoren * Diese Arbeit wird von der Sander Stiftung unterstützt.

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“…oIGF-I receptor, EGF receptor subtype 1 (HER1), EGF receptor subtype neu (HER2), EGF receptor subtype Erb-3 (HER3) and c-met [3][4][5][6][7][8]q, and of some proto-oncogenes, such as c-myc, H-ras, Ki-ras, c-Jun and c-fos [9][10][11][12], is strongly activated. p8 and these growth-promoting factors are probably induced to promote pancreatic regeneration.…”

Section: Introductionmentioning

confidence: 99%

Structural and functional characterization of the mouse p8 gene: promotion of transcription by the CAAT-enhancer binding protein α (C/EBPα) and C/EBPβ trans-acting factors involves a C/EBP cis-acting element and other regions of the promoter

Vasseur

Mallo

García‐Montero

et al. 1999

Biochemical Journal

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Rat p8 mRNA was discovered because of its strong activation in pancreas during the acute phase of pancreatitis. We report here structural and functional data on the mouse p8 gene. The mouse p8 polypeptide is 80 amino acids long and shows 91% and 75% identity with its rat and human counterparts respectively. The p8 gene is organized into three exons interrupted by two introns. Promoter regions involved in the regulation of p8 gene expression in NIH 3T3 cells were analysed. Chloramphenicol acetyltransferase (CAT) reporter assays with progressive deletions of the 5' flanking region of the mouse p8 gene revealed four silencer elements located from nucleotides -5000 to -1472, -1471 to -671, -670 to -473, and -239 to -117 respectively. One positive element was identified between nucleotides -117 and -72. We identified a CAAT-enhancer binding protein (C/EBP) cis-acting element at position -111. Site-directed mutagenesis of this consensus site decreased promoter activity to 5% of that of the wild-type. An electrophoretic mobility-shift assay, using an oligonucleotide probe corresponding to the C/EBP consensus and nuclear extracts of NIH 3T3 cells transfected with C/EBPalpha or C/EBPbeta expression vectors, generated specific DNA-protein complexes that were supershifted with specific antibodies against C/EBPalpha and C/EBPbeta. Co-transfection with C/EBPalpha or C/EBPbeta expression vectors and the p-116/+36p8-CAT construct increased the reporter gene activity in a dose-dependent fashion. Surprisingly, overexpression of C/EBPalpha or C/EBPbeta still increased the promoter activity of both pC/EBPmut-116/+36p8-CAT (which contains the C/EBP mutated site) and the p-71/+36-CAT construct (which does not contain the C/EBP site). Collectively, these results show that C/EBPalpha and C/EBPbeta trans-acting factors can promote transcription of the mouse p8 gene (i) by direct binding to the C/EBP consensus site, and (ii) by enhancing the activity of other trans-acting factors interacting with the p8 promoter.

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Expression of the Protooncogene jun Is Induced in the Rat Pancreas by Cerulein Infusion

Cited by 4 publications

References 0 publications

Localized pancreatic NF-κB activation and inflammatory response in taurocholate-induced pancreatitis

Localized pancreatic NF-κB activation and inflammatory response in taurocholate-induced pancreatitis

Die Bedeutung von Peptidhormonen des Magen-Darm-Trakts für das Wachstum von humanen gastrointestinalen Tumoren*

Structural and functional characterization of the mouse p8 gene: promotion of transcription by the CAAT-enhancer binding protein α (C/EBPα) and C/EBPβ trans-acting factors involves a C/EBP cis-acting element and other regions of the promoter

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