Molecular cloning of the mouse CCK gene: expression in different brain regions and during cortical development

Vitale, María; Vashishtha, Anshu; Linzer, E.; Powell, D. J.; Friedman, Jeffrey M.

doi:10.1093/nar/19.1.169

Cited by 27 publications

(7 citation statements)

References 46 publications

(28 reference statements)

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“…At confluence, RNA was extracted from the cell monolayer and the levels of CCK RNA were measured in an RNase protection assay specific for mouse and human CCK ( Fig. 2) (10,40). The labeled RNA probe was derived from the third exon of the mouse CCK gene.…”

Section: Resultsmentioning

confidence: 99%

Expression of the cholecystokinin gene in pediatric tumors.

Friedman

Vitale

Maimon

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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We have examined a wide range of cultured human tumor cell lines and found that a specific subset of tumors expresses the cholecystokinin (CCK) gene. All neuroepitheliomas (eight) and Ewing sarcoma (eight) cell lines that were tested express CCK RNA. In addition, two of six rhabdomyosarcoma cell lines also express the CCK gene, suggesting that rhabdomyosarcomas are probably heterogenous and that a subset may be similar to Ewing sarcoma and neuroepithelioma. Very few of the positive tumors express completely processed immunoreactive CCK. However, we have used a radioimmunoassay that detects the CCK precursor to demonstrate synthesis of CCK precursor-like peptides by all of the Ewing sarcoma and neuroepithelioma lines that were tested and by the rhabdomyosarcoma cell line that expresses CCK mRNA. These data demonstrate a consistent association of CCK gene expression with a specific group of human neoplasms. The data also add credence to the theory that Ewing sarcoma and neuroepithelioma are derived from the same transformed cell type. Finally, our results suggest that CCK gene expression may serve as a marker to distinguish these tumors, which are considered to be small-round-cell tumors of childhood, from other pediatric tumors.

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Section: Resultsmentioning

confidence: 99%

Expression of the cholecystokinin gene in pediatric tumors.

Friedman

Vitale

Maimon

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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“…Imaging and quantitation were performed on a GS‐250 Molecular Imager (Bio‐Rad). The CCK probe was a 0.8‐kb Bgl II fragment containing exon 3 isolated from a genomic clone described by Vitale et al [24]. After hybridization, filters were stripped and rehybridized with a mouse ribosomal protein L32 (rpL32) probe [25]to control for RNA loading.…”

Section: Methodsmentioning

confidence: 99%

Altered processing of procholecystokinin in carboxypeptidase E‐deficient fat mice: differential synthesis in neurons and endocrine cells

et al. 1998

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The fat mouse strain exhibits a late-onset obesity syndrome associated with a mutation in the gene encoding carboxypeptidase E (CPE). CPE plays a central role in the biosynthesis of many regulatory peptides. Therefore, we examined the processing of procholecystokinin (proCCK) in the brain (neurons) and small intestine (endocrine cells) of fat/fat mice. In the brain, bioactive CCK was markedly reduced (7.9 þ 1.0 pmol/g in fat/fat mice vs. 82.5 þ 11.2 pmol/g in controls), but the concentration of the CPE substrate, glycylarginine-extended CCK, was elevated 105-fold. In contrast, the concentration of bioactive CCK in intestinal endocrine cells was unaffected. Endocrine cell processing was, nevertheless, altered with a 33-fold increase in glycyl-arginine-extended CCK. Interestingly, although total proCCK products were normal in the brain they were elevated 3-fold in the intestine, indicating that biosynthesis is upregulated in endocrine cells but not neurons to compensate for the processing defect. These results demonstrate that the CPE mutation differentially affects CCK processing in these two cell types. Intestinal CCK synthesis more closely resembles progastrin processing, suggesting the presence of an endocrine-specific biosynthetic regulatory mechanism not present in neurons.z 1998 Federation of European Biochemical Societies.

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“…The first 100 bp 5Ј to the conventionally accepted transcription initiation site in rat (10,23), mouse (11), and man (16) have 80% homology. Sp1 consensus recognition sequence has been described in the human CCK promoter between Ϫ37 and Ϫ48 (16).…”

Section: Discussionmentioning

confidence: 99%

“…In the brain CCK is a neurotransmitter (8,9). There is a commonly accepted gut, as well as brain, CCK transcription initiation site in the rat (10), mouse (11), and man (12). Alternatively, more distal 5Ј CCK transcription start sites have been identified in the brain of the rat (13).…”

Section: Cholecystokinin (Cck)mentioning

confidence: 99%

Identification of Overlapping AP-2/NF-κB-responsive Elements on the Rat Cholecystokinin Gene Promoter

Katsel

Greenstein²

2001

Journal of Biological Chemistry

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In this study we evaluate both proximal and more distal transcriptional regulation of the 5 flanking region of the rat cholecystokinin gene in transfected GH3 (rat pituitary tumor) cells. Transcriptional activity was measured on the intact (؊400 to ؉73) 5 flanking region of cholecystokinin (CCK), as well as with DNA constructs, which were deleted in both the conventional 5 to 3, as well as an unconventional 3 to 5 direction. Our in vivo studies indicate complex phorbol ester and forskolin interactions in the 10-base pair region between ؊130 and ؊140. We conclude, there are at least two transcriptional factors involved in regulation of the rat CCK transcription in this region. In vitro studies utilizing heterologous nuclear (HeLa) extract, as well as purified transcription factors AP-2 and NF-B, identify overlapped AP-2-and NF-B-responsive elements within the 17-base pair sequence between ؊149 and ؊134 of the distal 5 flanking region. In this region complex transcriptional regulation occurs, which indicates inhibition of AP-2 CCK promoter complexing by NF-B. Sixpoint mutations introduced into this sequence prevent AP-2 and NF-B binding to CCK promoter, as well as its transcriptional activation by phorbol ester and forskolin in GH3 cells. Cholecystokinin (CCK),1 a prototypical brain-gut peptide (1-5), has hemacrine (3, 6) and autocrine (7) action in the gut. In the brain CCK is a neurotransmitter (8, 9). There is a commonly accepted gut, as well as brain, CCK transcription initiation site in the rat (10), mouse (11), and man (12). Alternatively, more distal 5Ј CCK transcription start sites have been identified in the brain of the rat (13). Transcriptional control of CCK is regulated by multiple factors. These include phorbol ester (14 -16), cAMP (14,(17)(18)(19)(20), and gonadal steroids (21), as well as glucocorticoids (22). Several cis-elements, important in transcriptional control, have been identified within the first 119 bp of the 5Ј flanking region of the rat CCK gene (10). This 119-bp fragment contains a sequence homologous with a 12-Otetradecanoylphorbol 13-acetate (TPA)-responsive element of the c-fos gene, as well as a cAMP-responsive element identified in the proenkephalin gene (23). This sequence binds several transcription factors including AP-1, jun, and fos homodimers, as well as cAMP-responsive element-binding protein (16,19). Two other recognition sites on the human CCK gene are Sp1 (at Ϫ39 to Ϫ34) and E-box or upstream stimulatory factor (at Ϫ97 to Ϫ92) (16). Additionally, a negative interaction was detected between TPA-responsive element and E-box or upstream stimulatory factor-responsive element (24).TPA and forskolin activate specific nuclear proteins, which regulate gene transcription. These proteins include AP-2 (25) and NF-B (26, 27). Transcription factor AP-2 is activated either directly or indirectly by two signal transduction pathways (25). One route involves cAMP-dependent protein kinase A. The other involves phorbol ester and diacylglycerol-activated protein kinase C (28). AP-2 specifi...

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Molecular cloning of the mouse CCK gene: expression in different brain regions and during cortical development

Cited by 27 publications

References 46 publications

Expression of the cholecystokinin gene in pediatric tumors.

Expression of the cholecystokinin gene in pediatric tumors.

Altered processing of procholecystokinin in carboxypeptidase E‐deficient fat mice: differential synthesis in neurons and endocrine cells

Identification of Overlapping AP-2/NF-κB-responsive Elements on the Rat Cholecystokinin Gene Promoter

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