CCK<sub>B</sub>/gastrin receptor mediates synergistic stimulation of DNA synthesis and cyclin D1, D3, and E expression in Swiss 3T3 cells

Zhukova, Elena; Sinnett‐Smith, James; Wong, Helen; Chiu, Terence

doi:10.1002/jcp.10018

Cited by 31 publications

(31 citation statements)

References 54 publications

(59 reference statements)

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“…Although the participation of G-17 in cellular proliferation is debatable, two recent studies have shown increased proliferation by G-17 in gastric cells (Hollande et al, 2001;Song et al, 2003). The fact that G-17 can induce cyclin D1 expression (Zhukova et al, 2001;Song et al, 2003) indirectly reveals its growth-promoting/ oncogenic function, since cyclin D1 functions as an oncogene in several kinds of tumor tissues (Motokura and Arnold, 1993), and new evidence suggests a role in invasion as well (Arato-Ohshima and Sawa, 1999;Jung et al, 2001). The CCK2 receptor (Watson et al, 2000) and gastrin (Bierkamp et al, 2002;Noble et al, 2003) have been implicated in regulating the invasion pathway as well.…”

Section: Discussionmentioning

confidence: 99%

“…A set of proteins known as cyclins (particularly cyclin D) contributes towards this process, by controlling G 1 /S transition, via regulating the activity of the cyclin-dependent kinases (CDK4 and CDK6) . Recent studies have shown increased expression of cyclin D1 in the presence of amidated gastrin (G-17) (Zhukova et al, 2001;Song et al, 2003), although the detailed mechanism(s) involved is unknown. In addition, H. pylori infection, which can lead to gastric cancer and is associated with hypergastrinemia also induces cyclin D1 transcription (Hirata et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

et al. 2004

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Gastrin and its precursors promote proliferation in different gastrointestinal cells. Since mature, amidated gastrin (G-17) can induce cyclin D1, we determined whether G-17-mediated induction of cyclin D1 transcription involved Wnt signaling and CRE-binding protein (CREB) pathways. Our studies indicate that G-17 induces protein, mRNA expression and transcription of the G 1 -specific marker cyclin D1, in the gastric adenocarcinoma cell line AGSE (expressing the gastrin/cholecystokinin B receptor). This was associated with an increase in steadystate levels of total and nonphospho b-catenin and its nuclear translocation, indicating the activation of the Wnt-signaling pathway. In addition, G-17-mediated increase in cyclin D1 transcription was significantly attenuated by axin or dominant-negative (dn) T-cell factor 4(TCF4), suggesting crosstalk of G-17 with the Wnt-signaling pathway. Mutational analysis indicated that this effect was mediated through the cyclic AMP response element (CRE) (predominantly) and the TCF sites in the cyclin D1 promoter, which was also inhibited by dnCREB. Furthermore, G-17 stimulation resulted in increased CRE-responsive reporter activity and CREB phosphorylation, indicating an activation of CREB. Chromatin immunoprecipitation studies revealed a G-17-mediated increase in the interaction of b-catenin with cyclin D1 CRE, which was attenuated by dnTCF4 and dnCREB. These results indicate that G-17 induces cyclin D1 transcription, via the activation of b-catenin and CREB pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

et al. 2004

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“…Cyclin D1 controls G1/S transition by regulating the activity of the cyclin-dependent kinases (CDK4 and CDK6) (22). Gastrin is known to activate expression of both c-fos (44) and cyclin D1 (40,56). To enable focus on endogenous gene regulation, we measured cyclin D1 and c-fos mRNA, and used RNA interference to knock down ICER.…”

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confidence: 99%

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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“…Like G17, epidermal growth factor (EGF) also stimulates the proliferation of gastric epithelial cells (19,20), and recently, the G17-related peptide CCK has been shown to synergize with EGF to stimulate DNA synthesis ([ 3 H]thymidine incorporation), cyclin-D3 expression, and retinoblastoma protein phosphorylation in cells expressing both CCK 2 R and EGF receptors (21). EGF and the related growth factors transforming growth factor-␣ and amphiregulin bind to a family of receptors known as type I receptor tyrosine kinases.…”

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confidence: 99%

Epidermal Growth Factor Potentiates Cholecystokinin/Gastrin Receptor-mediated Ca2+ Release by Activation of Mitogen-activated Protein Kinases

Olszewska-Pazdrak

Ives

Park

et al. 2004

Journal of Biological Chemistry

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2؉ ] i in the absence of G17. These data demonstrate that the activation state of the MEK1,2/ERK1,2 pathway can modulate the amplitude of the CCK 2 R-mediated Ca 2؉ release response and identify a novel mechanism for cross-talk between EGF receptor-and CCK 2 Rregulated signaling pathways.The gastrointestinal peptide hormone gastrin-(1-17) (G17) 1 plays an essential role in the regulation of digestion by stimulating gastric acid secretion, histamine synthesis and release, and proliferation of the gastric epithelium and endocrine pancreas (1, 2). In cancers of the stomach, pancreas, and colon, G17 promotes tumor cell proliferation, motility, and invasion (3-5). The biological effects of G17 are mediated by the cholecystokinin-2 (CCK 2 )/G17 receptor (CCK 2 R) (previously named CCK-B receptor), a member of the G protein-coupled receptor superfamily. Three splice variants of the CCK 2 R have been identified (6 -8) that bind the structurally related peptides cholecystokinin (CCK) and G17 with high affinities. An early event following agonist activation of CCK 2 R is the phospholipase C␤-mediated elaboration of inositol 1,4,5-triphosphate (6) from membrane phospholipids and the subsequent release of calcium (Ca 2ϩ ) from inositol 1,4,5-triphosphate-sensitive intracellular Ca 2ϩ stores.Calcium is an essential intracellular signal involved in many biological processes including fertilization, secretion, contraction, proliferation, differentiation, and apoptosis (9, 10). Small differences in the amplitude, duration, and/or temporal pattern of change in [Ca 2ϩ ] i can have profound effects on cell physiology, altering programs of gene expression (11, 12), secretory activity (13), cell proliferation, and survival (14 -16). Calcium is an essential signaling molecule in G17-stimulated cell proliferation. In Chinese hamster ovary cells expressing recombinant CCK 2 R, an agonist-induced increase in mitogen-activated protein kinase (MAPK) activity and [ 3 H]thymidine incorporation into DNA requires a slow oscillatory increase in [Ca 2ϩ ] i (17). In the rat pancreatic cancer cell line AR4-2J, a CCK 2 Rmediated increase in [Ca 2ϩ ] i is required for formation of the Shc-Grb2-Sos protein complex and subsequent activation of MAPK (18). Defining the molecular mechanisms involved in CCK 2 R regulation of [Ca 2ϩ ] i is necessary to understand the proliferative effects of G17 on normal and neoplastic cells.Like G17, epidermal growth factor (EGF) also stimulates the proliferation of gastric epithelial cells (19,20), and recently, the G17-related peptide CCK has been shown to synergize with EGF to stimulate DNA synthesis ([ 3 H]thymidine incorporation), cyclin-D3 expression, and retinoblastoma protein phosphorylation in cells expressing both CCK 2 R and EGF receptors (21). EGF and the related growth factors transforming growth factor-␣ and amphiregulin bind to a family of receptors known as type I receptor tyrosine kinases. This family is composed of four related receptors: the EGF receptor (EGFR/ErbB1/HER1), ErbB2 (HER2/neu), ErbB3 ...

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CCK_B/gastrin receptor mediates synergistic stimulation of DNA synthesis and cyclin D1, D3, and E expression in Swiss 3T3 cells

Cited by 31 publications

References 54 publications

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

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

Epidermal Growth Factor Potentiates Cholecystokinin/Gastrin Receptor-mediated Ca2+ Release by Activation of Mitogen-activated Protein Kinases

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CCKB/gastrin receptor mediates synergistic stimulation of DNA synthesis and cyclin D1, D3, and E expression in Swiss 3T3 cells

Cited by 31 publications

References 54 publications

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

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

Epidermal Growth Factor Potentiates Cholecystokinin/Gastrin Receptor-mediated Ca2+ Release by Activation of Mitogen-activated Protein Kinases

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CCK_B/gastrin receptor mediates synergistic stimulation of DNA synthesis and cyclin D1, D3, and E expression in Swiss 3T3 cells