Gastrin - Active participant or bystander in gastric carcinogenesis?

Nature Reviews Cancer

Volumn 6, Issue 12, 2006, Pages 936-946

  Watson, Susan A ^a   Grabowska, Anna M ^a   El Zaatari, Mohamad ^a   Takhar, Arjun ^a  

^a UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLECYSTOKININ B RECEPTOR; CHOLECYSTOKININ RECEPTOR BLOCKING AGENT; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; FLUOROURACIL; FOCAL ADHESION KINASE; FOLINIC ACID; G 17 DT; G PROTEIN COUPLED RECEPTOR; GASTRAZOLE; GASTRIN; GASTRIN 17; GASTRIN RELEASING PEPTIDE; GASTRIN RELEASING PEPTIDE RECEPTOR; HEPARIN BINDING EPIDERMAL GROWTH FACTOR; HISTAMINE; HORMONE DERIVATIVE; JB 5008; OCTREOTIDE; PROTEIN KINASE B; PROTON PUMP INHIBITOR; RC 3095; RECEPTOR BLOCKING AGENT; REGENERATING ISLET DERIVED 1ALPHA; SOMATOSTATIN; SOMATOSTATIN DERIVATIVE; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR CDX2; TRANSFORMING GROWTH FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VACCINE; VILLIN;

ANGIOGENESIS; APOPTOSIS; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER MODEL; CELL DIFFERENTIATION; CELL INVASION; CELL MOTILITY; CELL PROLIFERATION; CLINICAL EFFECTIVENESS; CLINICAL TRIAL; DISEASE ASSOCIATION; DRUG TARGETING; GENE EXPRESSION; HELICOBACTER INFECTION; HELICOBACTER PYLORI; HORMONAL REGULATION; HORMONE ACTION; HUMAN; NONHUMAN; PANCREAS CANCER; PRECANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; STOMACH ACID SECRETION; STOMACH ADENOCARCINOMA; STOMACH CANCER; STOMACH CARCINOGENESIS; STOMACH MUCOSA; TRANSGENIC MOUSE; UNSPECIFIED SIDE EFFECT;

ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; APOPTOSIS; CANCER VACCINES; CELL DIFFERENTIATION; CELL MOVEMENT; CELL TRANSFORMATION, NEOPLASTIC; GASTRIN-RELEASING PEPTIDE; GASTRINS; GENE EXPRESSION REGULATION, NEOPLASTIC; HELICOBACTER INFECTIONS; HUMANS; MICE; NEOPLASM INVASIVENESS; NEOPLASMS, EXPERIMENTAL; NEOVASCULARIZATION, PATHOLOGIC; PRECANCEROUS CONDITIONS; RISK FACTORS; SOMATOSTATIN; STOMACH NEOPLASMS;

EID: 33845255559     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc2014     Document Type: Review

References (173)

1. Wiborg, O. et al. Structure of a human gastrin gene. Proc. Natl Acad. Sci. USA 81, 1067-1069 (1984).
2. Dickinson, C. J., Sawada, M., Guo, Y. J., Finniss, S. & Yamada, T. Specificity of prohormone convertase endoproteolysis of progastrin in AtT-20 cells. J. Clin. Invest. 96, 1425-1431 (1995).
3. Marino, L. R., Takeuchi, T., Dickinson, C. J. & Yamada, T. Expression and post-translational processing of gastrin in heterologous endocrine cells. J. Biol. Chem. 266, 6133-6136 (1991).
4. Lloyd, K. C. Gut hormones in gastric function. Baillieres Clin. Endocrinol. Metab. 8, 111-136 (1994). This review provides a detailed overview of the interactions between gastrin, somatostatin and GRP on the maintenance of stomach homeostasis.
5. Soll, A. H. & Grossman, M. I. The interaction of stimulants on the function of isolated canine parietal cells. Philos. Trans. R. Soc. Lond. B 296, 5-15 (1981).
6. Obrink, K. J. Histamine and gastric acid secretion. A review. Scand. J. Gastroenterol. Suppl. 180, 4-8 (1991).
7. Walsh, J. H. Physiology and pathophysiology of gastrin. Mt Sinai J. Med. 59, 117-124 (1992).
8. Chuang, C. N., Tanner, M., Chen, M. C., Davidson, S. & Soll, A. H. Gastrin induction of histamine release from primary cultures of canine oxyntic mucosal cells. Am. J. Physiol. 263, G460-G465 (1992).
9. Waldum, H. L. et al. The cellular localization of the cholecystokinin 2 (gastrin) receptor in the stomach. Pharmacol. Toxicol. 91, 359-362 (2002).
10. Lindstrom, E., Chen, D., Norlen, P., Andersson, K. & Hakanson, R. Control of gastric acid secretion:the gastrin-ECL cell-parietal cell axis. Comp. Biochem. Physiol. 128, 505-514 (2001).
11. Komazawa, Y. et al. Tolerance to famotidine and ranitidine treatment after 14 days of administration in healthy subjects without Helicobacter pylori infection. J. Gastroenterol. Hepatol. 18, 678-682 (2003).
12. Soll, A. H., Amirian, D. A., Thomas, L. P., Reedy, T. J. & Elashoff, J. D. Gastrin receptors on isolated canine parietal cells. J. Clin. Invest. 73, 1434-1447 (1984).
13. Helander, H. F., Wong, H., Poorkhalkali, N. & Walsh, J. H. Immunohistochemical localization of gastrin/CCK-B receptors in the dog and guinea-pig stomach. Acta Physiol. Scand. 159, 313-320 (1997).
14. Kopin, A. S. et al. Expression cloning and characterization of the canine parietal cell gastrin receptor. Proc. Natl Acad. Sci. USA 89, 3605-3609 (1992).
15. Cabero, J. L., Li, Z. Q. & Mardh, S. Gastrin potentiates histamine-stimulated aminopyrine accumulation in isolated rat parietal cells. Am. J. Physiol. 261, G621-G627 (1991).
16. Brenna, E. & Waldum, H. L. Studies of isolated parietal and enterochromaffin-like cells from the rat. Scand. J. Gastroenterol. 26, 1295-1306 (1991).
17. Kobayashi, T. et al. Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor-deficient mice. J. Clin. Invest. 105, 1741-1749 (2000).
18. Karnik, P. S. & Wolfe, M. M. Somatostatin stimulates gastrin mRNA turnover in dog antral mucosa. J. Biol. Chem. 265, 2550-2555 (1990).
19. Godley, J. M. & Brand, S. J. Regulation of the gastrin promoter by epidermal growth factor and neuropeptides. Proc. Natl Acad. Sci. USA 86, 3036-3040 (1989).
20. Park, J., Chiba, T. & Yamada, T. Mechanisms for direct inhibition of canine gastric parietal cells by somatostatin. J. Biol. Chem. 262, 14190-14196 (1987).
21. Prinz, C., Sachs, G., Walsh, J. H., Coy, D. H. & Wu, S. V. The somatostatin receptor subtype on rat enterochromaffinlike cells. Gastroenterology 107, 1067-1074 (1994).
22. Allen, J. P. et al. Identification of cells expressing somatostatin receptor 2 in the gastrointestinal tract of Sstr2 knockout/lacZ knockin mice. J. Comp. Neurol. 454, 329-340 (2002).
23. Reeve, J. R. Jr et al. Amino acid sequences of three bombesin-like peptides from canine intestine extracts. J. Biol. Chem. 258, 5582-5588 (1983).
24. Sugano, K., Park, J., Soll, A. H. & Yamada, T. Stimulation of gastrin release by bombesin and canine gastrin-releasing peptides. Studies with isolated canine G cells in primary culture. J. Clin. Invest. 79, 935-942 (1987).
25. Schubert, M. L., Hightower, J., Coy, D. H. & Makhlouf, G. M. Regulation of acid secretion by bombesin/GRP neurons of the gastric fundus. Am. J. Physiol. 260, G156-G160 (1991).
26. Hohenberger, P. & Gretschel, S. Gastric cancer. Lancet 362, 305-315 (2003).
27. La Vecchia, C., Negri, E., Franceschi, S. & Gentile, A. Family history and the risk of stomach and colorectal cancer. Cancer 70, 50-55 (1992).
28. Lauren, P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol. Microbiol. Scand. 64, 31-49 (1965).
29. Miyaji, H. et al. Helicobacter pylori infection occurs via close contact with infected individuals in early childhood. J. Gastroenterol. Hepatol. 15, 257-262 (2000).
30. Wang, L. D. et al. Changes in p53 and cyclin D1 protein levels and cell proliferation in different stages of human esophageal and gastric-cardia carcinogenesis. Int. J. Cancer 59, 514-519 (1994).
31. Takaishi, S. et al. Synergistic inhibitory effects of gastrin and histamine receptor antagonists on Helicobacter-induced gastric cancer. Gastroenterology 128, 1965-1983 (2005).
32. Delle Fave, G., Capurso, G., Milione, M. & Panzuto, F. Endocrine tumours of the stomach. Best Pract. Res. Clin. Gastroenterol. 19, 659-673 (2005).
33. Sekikawa, A. et al. REG Iα protein may function as a trophic and/or anti-apoptotic factor in the development of gastric cancer. Gastroenterology 128, 642-653 (2005).
34. Kazumori, H., Ishihara, S., Fukuda, R. & Kinoshita, Y. Localization of REG receptor in rat fundic mucosa. J. Lab. Clin. Med. 139, 101-108 (2002).
35. Fukui, H. et al. Regenerating gene protein may mediate gastric mucosal proliferation induced by hypergastrinemia in rats. Gastroenterology 115, 1483-1493 (1998).
36. Miyaoka, Y. et al. Transgenic overexpression of REG protein caused gastric cell proliferation and differentiation along parietal cell and chief cell lineages. Oncogene 23, 3572-3579 (2004).
37. Berman, D. M. et al. Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours. Nature 425, 846-851 (2003). This study confirmed that the hedgehog pathway is essential for tumour growth through the induction of ligand expression and that this proliferation could be suppressed by the hedgehog pathway antagonist cyclopamine.
38. Osawa, H. et al. Sonic hedgehog stimulates the proliferation of rat gastric mucosal cells through ERK activation by elevating intracellular calcium concentration. Biochem. Biophys. Res. Commun. 344, 680-687 (2006).
39. Ma, X. et al. Frequent activation of the hedgehog pathway in advanced gastric adenocarcinomas. Carcinogenesis 26, 1698-1705 (2005).
40. Zavros, Y. et al. Gastrin-induced pepsinogen regulates sonic hedgehog processing and prevents gastric atrophy. Gastroenterology 130, A17 (2006).
41. Todisco, A. et al. Molecular mechanisms for the antiapoptotic action of gastrin. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G298-G307 (2001). This paper overviews the signalling pathways through which gastrin can mediate anti-apoptotic activity in cancer.
42. Todisco, A. et al. Functional role of protein kinase B/AKT in gastric acid secretion. J. Biol. Chem. 276, 46436-46444 (2001).
43. Riobo, N. A., Lu, K., Ai, X., Haines, G. M. & Emerson, C. P. Jr. Phosphoinositide 3-kinase and AKT are essential for sonic hedgehog signaling. Proc. Natl Acad. Sci. USA 103, 4505-4510 (2006).
44. Stepan, V. et al. Regulation and function of the sonic hedgehog signal transduction pathway in isolated gastric parietal cells. J. Biol. Chem. 280, 15700-15708 (2005).
45. Dimmler, A. et al. Transcription of sonic hedgehog, a potential factor for gastric morphogenesis and gastric mucosa maintenance, is up-regulated in acidic conditions. Lab. Invest. 83, 1829-1837 (2003).
46. Wang, T. C. et al. Synergistic interaction between hypergastrinemia and Helicobacter infection in a mouse model of gastric cancer. Gastroenterology 118, 36-47 (2000). This is a milestone publication highlighting that Helicobacter infection and hypergastrinaemia interact during the development of gastric cancer.
47. Zavros, Y. et al. Chronic gastritis in the hypochlorhydric gastrin-deficient mouse progresses to adenocarcinoma. Oncogene 24, 2354-2366 (2005).
48. Helicobacter & Cancer Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut 49, 347-353 (2001).
49. Beales, I. et al. Effect of Helicobacter pylori products and recombinant cytokines on gastrin release from cultured canine G cells. Gastroenterology 113, 465-471 (1997). This study was the first to show that H. pylori products might contribute indirectly to hypergastrinaemia through the induction of cytokines that go on to potentiate gastrin release from the G cell.
50. Suzuki, T. et al. TNF-α and interleukin 1 activate gastrin gene expression via MAPK- and PKC-dependent mechanisms. Am. J. Physiol. Gastrointest. Liver Physiol. 281, G1405-G1412 (2001).
51. Beales, I. L. Gastrin and interleukin-1β stimulate growth factor secretion from cultured rabbit gastric parietal cells. Life Sci. 75, 2983-2995 (2004).
52. Dockray, G. J., Varro, A., Dimaline, R. & Wang, T. The gastrins: their production and biological activities. Annu. Rev. Physiol. 63, 119-139 (2001).
53. Kinoshita, Y. & Ishihara, S. Mechanism of gastric mucosal proliferation induced by gastrin. J. Gastroenterol. Hepatol. 15, D7-D11 (2000).
54. Zavros, Y. et al. Treatment of Helicobacter gastritis with IL-4 requires somatostatin. Proc. Natl Acad. Sci. USA 100, 12944-12949 (2003).
55. Kao, J. Y. et al. Somatostatin inhibits dendritic cell responsiveness to Helicobacter pylori. Regul. Pept. 134, 23-29 (2006).
56. Takhar, A., Eremin, O. & Watson, S. A. The role of gastrin in dendritic cell function. Br. J. Surg. 93 (Suppl. 3), A15 (2006).
57. Makarenkova, V. P. et al. Lung cancer-derived bombesin-like peptides down-regulate the generation and function of human dendritic cells. J. Neuroimmunol. 145, 55-67 (2003).
58. Rieder, G., Merchant, J. L. & Haas, R. Helicobacter pylori cag-type IV secretion system facilitates corpus colonization to induce precancerous conditions in Mongolian gerbils. Gastroenterology 128, 1229-12242 (2005). This is a milestone paper defining a potential mechanism through which H. pylori can directly activate gastrin gene transcription by the G cell and also might indicate a way through which non-endocrine malignant cells could gain an activated gastrin gene.
59. Walter, P., Gilmore, R. & Blobel, G. Protein translocation across the endoplasmic reticulum. Cell 38, 5-8 (1984).
60. Burgess, T. L. & Kelly, R. B. Constitutive and regulated secretion of proteins. Annu. Rev. Cell Biol. 3, 243-293 (1987).
61. Calam, J., Dockray, G. J., Walker, R., Tracy, H. J. & Owens, D. Molecular forms of gastrin in peptic ulcer: comparison of serum and tissue concentrations of G17 and G34 in gastric and duodenal ulcer subjects. Eur. J. Clin. Invest. 10, 241-247 (1980).
62. Dickinson, C. J., Daugherty, D., Guo, Y. J., Hughes, P. & Yamada, T. Molecular analysis of dibasic endoproteolytic cleavage signals. J. Biol. Chem. 267, 21795-21801 (1992).
63. Dickson, J., Grabowska, A., Atherton, J. & Watson, S. A. Role of gastrin in Helicobacter pylori induced HB-EGF gene up-regulation and ectodomain shedding. Gastroenterology 126, A59 (2004).
64. Dickson, J. H., Atherton, J. & Watson, S. A. Helicobacter pylori may up-regulate gastrin/CCK-2 receptor expression in exposed cells and human gastric mucosa. Gastroenterology 128, W1341 (2005).
65. Brzozowski, T. et al. Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression, apoptosis, and functional gastric mucosal impairment in Helicobacter pylori-infected Mongolian gerbils. Helicobacter 11, 10-20 (2006).
66. Piotrowski, J., Skrodzka, D., Slomiany, A. & Slomiany, B. L. Reversal of gastric somatostatin receptor inhibition by Helicobacter pylori lipopolysaccharide with ebrotidine and sulglycotide. Gen. Pharmacol. 28, 705-708 (1997).
67. Guillermet, J. et al. Somatostatin receptor subtype 2 sensitizes human pancreatic cancer cells to death ligand-induced apoptosis. Proc. Natl Acad. Sci. USA 100, 155-160 (2003).
68. Beales, I. L. Effect of platelet-activating factor on gastrin release from cultured rabbit G-cells. Dig. Dis. Sci. 46, 301-306 (2001).
69. Li, H. C., Stoicov, C., Rogers, A. B. & Houghton, J. Stem cells and cancer: evidence for bone marrow stem cells in epithelial cancers. World J. Gastroenterol. 12, 363-371 (2006).
70. Kanda, N. et al. Involvement of cyclooxygenase-2 in gastric mucosal hypertrophy in gastrin transgenic mice. Am. J. Physiol. Gastrointest. Liver Physiol. 290, G519-G527 (2006).
71. Jensen, R. T. Consequences of long-term proton pump blockade: insights from studies of patients with gastrinomas. Basic Clin. Pharmacol. Toxicol. 98, 4-19 (2006).
72. Laine, L., Ahnen, D., McClain, C., Solcia, E. & Walsh, J. H. Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibi-tors. Aliment. Pharmacol. Ther. 14, 651-668 (2000).
73. Mattsson, H. et al. Partial gastric corpectomy results in hypergastrinemia and development of gastric enterochromaffinlike-cell carcinoids in the rat. Gastroenterology 100, 311-319 (1991).
74. Havu, N. Enterochromaffin-like cell carcinoids of gastric mucosa in rats after life-long inhibition of gastric secretion. Digestion 35, 42-55 (1986).
75. Havu, N., Mattsson, H., Ekman, L. & Carlsson, E. Enterochromaffin- like cell carcinoids in the rat gastric mucosa following long-term administration of ranitidine. Digestion 45, 189-195 (1990).
76. Hakanson, R. et al. Effects of antrectomy or portacaval shunting on the histamine-storing endocrine-like cells in oxyntic mucosa of rat stomach. A fluorescence histochemical, electron microscopic and chemical study. J. Physiol. 259, 785-800 (1976).
77. Simonsson, M. et al. Endocrine cells in the human oxyntic mucosa. A histochemical study. Scand. J. Gastroenterol. 23, 1089-1099 (1988).
78. Varro, A. et al. Processing of the gastrin precursor. Modulation of phosphorylated, sulfated, and amidated products. J. Biol. Chem. 265, 21476-21481 (1990).
79. Azuma, T., Taggart, R. T. & Walsh, J. H. Effects of bombesin on the release of glycine-extended progastrin (gastrin G) in rat antral tissue culture. Gastroenterology 93, 322-329 (1987).
80. Huebner, V. D. et al. Purification and structural characterization of progastrin-derived peptides from a human gastrinoma. J. Biol. Chem. 266, 12223-12227 (1991).
81. Azuma, T. et al. Carboxyl terminal glycine extended progastrin (gastrin-G) in gastric antral mucosa of patients with gastric or duodenal ulcer and in gastrinomas. J. Gastroenterol. Hepatol. 5, 525-529 (1990).
82. Chen, D. et al. Glycine-extended gastrin synergizes with gastrin-17 to stimulate acid secretion in gastrin deficient mice. Gastroenterology 116, 756-765 (1999).
83. Kuipers, E. J. et al. Cure of Helicobacter pylori infection in patients with reflux oesophagitis treated with long term omeprazole reverses gastritis without exacerbation of reflux disease: results of a randomised controlled trial. Gut 53, 12-20 (2004).
84. Eissele, R., Brunner, G., Simon, B., Solcia, E. & Arnold, R. Gastric mucosa during treatment with lansoprazole: Helicobacter pylori is a risk factor for argyrophil cell hyperplasia. Gastroenterology 112, 707-717 (1997).
85. Uemura, N. et al. Helicobacter pylori infection and the development of gastric cancer. N. Engl. J. Med. 345, 784-789 (2001).
86. Gillen, D. & McColl, K. E. Problems associated with the clinical use of proton pump inhibitors. Pharmacol. Toxicol. 89, 281-286 (2001).
87. Borch, K., Renvall, H., Liedberg, G. & Andersen, B. N. Relations between circulating gastrin and endocrine cell proliferation in the atrophic gastric fundic mucosa. Scand. J. Gastroenterol. 21, 357-363 (1986).
88. Solcia, E., Fiocca, R., Villani, L., Luinetti, O. & Capella, C. Hyperplastic, dysplastic, and neoplastic enterochromaffin-like-cell proliferations of the gastric mucosa. Classification and histogenesis. Am. J. Surg. Pathol. 19, S1-S7 (1995).
89. Delle Fave, G. et al. Hypergastrinemia and enterochromaffin-like cell hyperplasia. Yale J. Biol. Med. 71, 291-301 (1998).
90. Fich, A., Talley, N. J., Shorter, R. G. & Phillips, S. F. Zollinger-Ellison syndrome. Relation to Helicobacter pylori-associated chronic gastritis and gastric acid secretion. Dig. Dis. Sci. 36, 10-14 (1991).
91. Saeed, Z. A. et al. Helicobacter pylori and Zollinger-Ellison syndrome. Dig. Dis. Sci. 36, 15-18 (1991).
92. Weber, H. C., Venzon, D. J., Jensen, R. T. & Metz, D. C. Studies on the interrelation between Zollinger-Ellison syndrome, Helicobacter pylori, and proton pump inhibitor therapy. Gastroenterology 112, 84-91 (1997).
93. Hirschowitz, B. I. & Haber, M. M. Helicobacter pylori effects on gastritis, gastrin and enterochromaffin-like cells in Zollinger-Ellison syndrome and non-Zollinger-Ellison syndrome acid hypersecretors treated long-term with lansoprazole. Aliment. Pharmacol. Ther. 15, 87-103 (2001).
94. Peghini, P. L. et al. Effect of chronic hypergastrinemia on human enterochromaffin-like cells: insights from patients with sporadic gastrinomas. Gastroenterology 123, 68-85 (2002).
95. El-Zimaity, H. M., Ota, H., Graham, D. Y., Akamatsu, T. & Katsuyama, T. Patterns of gastric atrophy in intestinal type gastric carcinoma. Cancer 94, 1428-1436 (2002).
96. Otsuka, T. et al. Coexistence of gastric- and intestinal-type endocrine cells in gastric and intestinal mixed intestinal metaplasia of the human stomach. Pathol. Int. 55, 170-179 (2005).
97. Correa, P. Chronic gastritis: a clinico-pathological classification. Am. J. Gastroenterol. 83, 504-509 (1988).
98. Henwood, M., Clarke, P. A., Smith, A. M. & Watson, S. A. Expression of gastrin in developing gastric adenocarcinoma. Br. J. Surg. 88, 564-568 (2001).
99. Watson, S. A., Morris, T. M., Varro, A., Michaeli, D. & Smith, A. M. A comparison of the therapeutic effectiveness of gastrin neutralisation in two human gastric cancer models: relation to endocrine and autocrine/paracrine gastrin mediated growth. Gut 45, 812-817 (1999).
100. Koh, T. J. & Chen, D. Gastrin as a growth factor in the gastrointestinal tract. Regul. Pept. 93, 37-44 (2000).
101. Hur, K. et al. Expression of gastrin and its receptor in human gastric cancer tissues. J. Cancer Res. Clin. Oncol. 132, 85-91 (2006). This is the most comprehensive study to date examining co-expression of gastrin and the CCK2 receptor on human gastric cancer tissues, including evaluation of their relationship to grade, sex and prognosis.
102. Merchant, J. L., Du, M. & Todisco, A. SP1 phosphorylation by ERK 2 stimulates DNA binding. Biochem. Biophys. Res. Commun. 254, 454-461 (1999).
103. Murayama, Y. et al. Localization of heparin-binding epidermal growth factor-like growth factor in human gastric mucosa. Gastroenterology 109, 1051-1059 (1995).
104. Madtes, D. K., Malden, L. T., Raines, E. W. & Ross, R. Induction of transcription and secretion of TGF-α by activated human monocytes. Chest 99, S79 (1991).
105. Mortensen, E. R., Marks, P. A., Shiotani, A. & Merchant, J. L. Epidermal growth factor and okadaic acid stimulate SP1 proteolysis. J. Biol. Chem. 272, 16540-16547 (1997).
106. Todisco, A., Seva, C., Takeuchi, Y., Dickinson, C. J. & Yamada, T. Somatostatin inhibits AP-1 function via multiple protein phosphatases. Am. J. Physiol. 269, G160-G166 (1995).
107. Bachwich, D., Merchant, J. & Brand, S. J. Identification of a cis-regulatory element mediating somatostatin inhibition of epidermal growth factor-stimulated gastrin gene transcription. Mol. Endocrinol. 6, 1175-1184 (1992).
108. Merchant, J. L. et al. ZBP-89, a Kruppel-like zinc finger protein, inhibits epidermal growth factor induction of the gastrin promoter. Mol. Cell. Biol. 16, 6644-6653 (1996).
109. Law, G. L. et al. Transcription factor ZBP-89 regulates the activity of the ornithine decarboxylase promoter. J. Biol. Chem. 273, 19955-19964 (1998).
110. Merchant, J. L., Tucker, T. P. & Zavros, Y. in Gastrin in the New Millennium (eds Merchant, J. L., Buchan, A. M. J. & Wang, T. C.) 55-70 (CURE Foundation, 2004).
111. Bai, L. & Merchant, J. L. ZBP-89 promotes growth arrest through stabilization of p53. Mol. Cell. Biol. 21, 4670-4683 (2001).
112. Koh, T. J. et al. Gastrin is a target of the β-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis. J. Clin. Invest. 106, 533-539 (2000).
113. Zhang, Q. X., Dou, Y. L., Shi, X. Y. & Ding, Y. Expression of somatostatin mRNA in various differentiated types of gastric carcinoma. World J. Gastroenterol. 4, 48-51 (1998).
114. Patel, O., Shulkes, A. & Baldwin, G. S. Gastrin-releasing peptide and cancer. Biochim. Biophys. Acta 1766, 23-41 (2006).
115. Hu, C. et al. The effect of somatostatin and SSTR3 on proliferation and apoptosis of gastric cancer cells. Cancer Biol. Ther. 3, 726-730 (2004).
116. Preston, S. R., Woodhouse, L. F., Jones-Blackett, S., Wyatt, J. I. & Primrose, J. N. High affinity binding sites for gastrin releasing peptide on human gastric cancer and Menetrier's mucosa. Cancer Res. 53, 5090-5092 (1993).
117. Carroll, R. E., Carroll, R. & Benya, R. V. Characterization of gastrin-releasing peptide receptors aberrantly expressed by non-antral gastric adenocarcinomas. Peptides 20, 229-237 (1999). This paper shows that mutated isoforms of the GRP receptor are expressed by non-antral gastric adenocarcinoma.
118. Ramamoorthy, S., Stepan, V. & Todisco, A. Intracellular mechanisms mediating the anti-apoptotic action of gastrin. Biochem. Biophys. Res. Commun. 323, 44-48 (2004).
119. Ogasa, M. et al. Gastrin activates nuclear factor κB (NFκB) through a protein kinase C dependent pathway involving NFκB inducing kinase, inhibitor κB (IκB) kinase, and tumour necrosis factor receptor associated factor 6 (TRAF6) in MKN-28 cells transfected with gastrin receptor. Gut 52, 813-819 (2003).
120. Harris, J. C., Clarke, P. A., Awan, A., Jankowski, J. & Watson, S. A. An antiapoptotic role for gastrin and the gastrin/CCK-2 receptor in Barrett's esophagus. Cancer Res. 64, 1915-1919 (2004).
121. Harris, J. C., Clarke, P. & Watson, S. A. Gastrin mediated XIAP up-regulation and associated cisplatin resistance in the pre-malignant and malignant oesophagus. Gastroenterology 128 (Suppl. 3), A42 (2005).
122. Mao, J. D. et al. Correlation between expression of gastrin, somatostatin and cell apoptosis regulation gene BCL-2/BAX in large intestine carcinoma. World J. Gastroenterol. 11, 721-725 (2005).
123. Ferjoux, G. et al. Signal transduction of somatostatin receptors negatively controlling cell proliferation. J. Physiol. Paris 94, 205-210 (2000). This study defines how somatostatin receptor subtypes can mediate distinct signal-transduction pathways that inhibit proliferation, induce cell-cycle arrest and promote angiogenesis.
124. Sharma, K., Patel, Y. C. & Srikant, C. B. Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3. Mol. Endocrinol. 10, 1688-1696 (1996).
125. Theodoropoulou, M. et al. Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumor cells by altering phosphatidylinositol 3-kinase signaling and inducing Zac1 expression. Cancer Res. 66, 1576-1582 (2006).
126. Qiao, J., Kang, J., Cree, J., Evers, B. M. & Chung, D. H. Gastrin-releasing peptide-induced down-regulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten) in neuro-blastomas. Ann. Surg. 241, 684-691; discussion 691-692 (2005).
127. Kinoshita, Y., Ishihara, S., Kadowaki, Y., Fukui, H. & Chiba, T. REG protein is a unique growth factor of gastric mucosal cells. J. Gastroenterol. 39, 507-513 (2004).
128. Fukui, H. et al. Effects of Helicobacter pylori infection on the link between regenerating gene expression and serum gastrin levels in Mongolian gerbils. Lab. Invest. 83, 1777-1786 (2003).
129. Pradeep, A. et al. Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells. Oncogene 23, 3689-3699 (2004).
130. Song, D. H. et al. Gastrin stabilises β-catenin protein in mouse colorectal cancer cells. Br. J. Cancer 92, 1581-1587 (2005).
131. Franco, A. T. et al. Activation of β-catenin by carcinogenic Helicobacter pylori. Proc. Natl Acad. Sci. USA 102, 10646-10651 (2005).
132. Wu, P. et al. Correlation between the expressions of gastrin, somatostatin and cyclin and cyclin-depend kinase in colorectal cancer. World J. Gastroenterol. 11, 7211-7217 (2005).
133. Xiao, D., Chinnappan, D., Pestell, R., Albanese, C. & Weber, H. C. Bombesin regulates cyclin D1 expression through the early growth response protein EGR-1 in prostate cancer cells. Cancer Res. 65, 9934-9942 (2005).
134. Tsutsui, S. et al. Induction of heparin binding epidermal growth factor-like growth factor and amphiregulin mRNAs by gastrin in the rat stomach. Biochem. Biophys. Res. Commun. 235, 520-523 (1997).
135. Miyazaki, Y. et al. Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor. Gastroenterology 116, 78-89 (1999).
136. Tokunaga, A. et al. Clinical significance of epidermal growth factor (EGF), EGF receptor, and c-erbB-2 in human gastric cancer. Cancer 75, 1418-1425 (1995).
137. Thomas, S. M. et al. Gastrin-releasing peptide receptor mediates activation of the epidermal growth factor receptor in lung cancer cells. Neoplasia 7, 426-431 (2005).
138. Clarke, P. A., Dickson, J. H., Harris, J. C., Grabowska, A. & Watson, S. A. Gastrin enhances the angiogenic potential of endothelial cells via modulation of heparin binding epidermal-like growth factor. Cancer Res. 66, 3504-3512 (2006).
139. Guo, Y. S. et al. Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways. Evidence for involvement of ERK5 kinase and transactivation of the epidermal growth factor receptor. J. Biol. Chem. 277, 48755-48763 (2002).
140. Abdalla, S. I. et al. Gastrin-induced cyclooxygenase-2 expression in Barrett's carcinogenesis. Clin. Cancer Res. 10, 4784-4792 (2004).
141. Colucci, R. et al. Gastrin promotes human colon cancer cell growth via CCK-2 receptor-mediated cyclooxygenase-2 induction and prostaglandin E2 production. Br. J. Pharmacol. 144, 338-348 (2005).
142. Sun, W. H. et al. Expression of cyclooxygenase-2 and matrix metalloproteinase-9 in gastric carcinoma and its correlation with angiogenesis. Jpn J. Clin. Oncol. 35, 707-713 (2005).
143. Woltering, E. A. Development of targeted somatostatin-based antiangiogenic therapy: a review and future perspectives. Cancer Biother. Radiopharm. 18, 601-609 (2003).
144. Florio, T. et al. Somatostatin inhibits tumor angiogenesis and growth via somatostatin receptor-3-mediated regulation of endothelial nitric oxide synthase and mitogen-activated protein kinase activities. Endocrinology 144, 1574-1584 (2003).
145. Reubi, J. C. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr. Rev. 24, 389-427 (2003).
146. Levine, L. et al. Bombesin stimulates nuclear factor κB activation and expression of proangiogenic factors in prostate cancer cells. Cancer Res. 63, 3495-3502 (2003).
147. Ferrand, A. et al. Involvement of JAK2 upstream of the PI 3-kinase in cell-cell adhesion regulation by gastrin. Exp. Cell Res. 301, 128-138 (2004).
148. He, H., Pannequin, J., Tantiongco, J. P., Shulkes, A. & Baldwin, G. S. Glycine-extended gastrin stimulates cell proliferation and migration through a Rho- and ROCK-dependent pathway, not a Rac/Cdc42-dependent pathway. Am. J. Physiol. Gastrointest. Liver Physiol. 289, G478-G488 (2005).
149. B receptor promotes branching morphogenesis in gastric AGS cells. Am. J. Physiol. Gastrointest. Liver Physiol. 283, G292-G299 (2002).
150. Wroblewski, L. E., Pritchard, D. M., Carter, S. & Varro, A. Gastrin-stimulated gastric epithelial cell invasion: the role and mechanism of increased matrix metalloproteinase 9 expression. Biochem. J. 365, 873-879 (2002).
151. Chau, I. et al. Gastrazole (JB95008), a novel CCK2/gastrin receptor antagonist, in the treatment of advanced pancreatic cancer: results from two randomised controlled trials. Br. J. Cancer 94, 1107-11015 (2006).
152. Watson, S. A. et al. Gastrimmune raises antibodies that neutralize amidated and glycine-extended gastrin-17 and inhibit the growth of colon cancer. Cancer Res. 56, 880-885 (1996).
153. Gilliam, A. D. et al. A phase II study of G17DT in gastric carcinoma. Eur. J. Sur. Oncol. 30, 536-543 (2004).
154. Ajani, J. A. et al. An open-label, multinational, multicenter study of G17DT vaccination combined with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or gastroesophageal cancer: the GC4 study. Cancer 106, 1908-1916 (2006).
155. Schwartsmann, G. et al. A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies. Invest. New Drugs 24, 403-412 (2006).
156. Reubi, J. C., Waser, B., Schaer, J. C. & Laissue, J. A. Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur. J. Nucl. Med. 28, 836-846 (2001). This remains the most comprehensive assessment of 'functional' somatostatin isoforms expressed by human gastric adenocarcinoma specimens.
157. Ferrand, A. & Wang, T. C. Gastrin and cancer: a review. Cancer Lett. 238, 15-29 (2005).
158. Asaka, M., Kudo, M., Kato, M., Sugiyama, T. & Takeda, H. Review article: long-term Helicobacter pylori infection - from gastritis to gastric cancer. Aliment. Pharmacol. Ther. 12, 9-15 (1998).
159. Dimaline, R. & Sandvik, A. K. Histidine decarboxylase gene expression in rat fundus is regulated by gastrin. FEBS Lett. 281, 20-22 (1991).
160. Fykse, V., Coy, D. H., Waldum, H. L. & Sandvik, A. K. Somatostatin-receptor 2 (sst2)-mediated effects of endogenous somatostatin on exocrine and endocrine secretion of the rat stomach. Br. J. Pharmacol. 144, 416-421 (2005).
161. Bakke, I., Qvigstad, G., Sandvik, A. K. & Waldrum, H. L. The CCK-2 receptor is located on the ECL cell, but not on the parietal cell. Scand. J. Gastroenterol. 11, 1128-1133 (2001).
162. Nakajima, T. et al. Gastrin stimulates the growth of gastric pit cell precursors by inducing its own receptors. Am. J. Physiol. Gastrointest. Liver Physiol. 282, G359-G366 (2002).
163. Schmidt, W. E. & Schmitz, F. Cellular localization of cholecystokinin receptors as the molecular basis of the periperal regulation of acid secretion. Pharmacol. Toxicol. 91, 351-358 (2002).
164. Schmitz, F. et al. CCK-B/gastrin receptors in human colorectal cancer. Eur. J. Clin. Invest. 31, 812-820 (2001).
165. Ito, M. et al. Functional characterization of two cholecystokinin-B/ gastrin receptor isoforms: a preferential splice donor site in the human receptor gene. Cell Growth Differ. 5, 1127-1135 (1994).
166. Zhou, J. et al. Human gastric tissues coexpress two different splicing cholecystokinin-B/gastrin receptors. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 21, 440-443 (2004).
167. Miyake, A. A truncated isoform of human CCK-B/ gastrin receptor generated by alternative usage of a novel exon. Biochem. Biophys. Res. Commun. 208, 230-237 (1995).
168. Laghi, L. et al. Frameshift mutations of human gastrin receptor gene (hGARE) in gastrointestinal cancers with microsatellite instability. Lab. Invest. 82, 265-271 (2002).
169. Gugger, M., Waser, B., Kappeler, A., Schonbrunn, A. & Reubi, J. C. Cellular detection of sst2A receptors in human gastrointestinal tissue. Gut 53, 1431-1436 (2004).
170. van der Hoek, J., Hofland, L. J. & Lamberts, S. W. Novel subtype specific and universal somatostatin analogues: clinical potential and pitfalls. Curr. Pharm. Des. 11, 1573-1592 (2005).
171. Panteris, V. & Karamanolis, D. G. The puzzle of somatostatin: action, receptors, analogues and therapy. Hepatogastroenterology 52, 1771-1781 (2005).
172. Alderton, F., Fan, T. P., Schindler, M. & Humphrey, P. P. Rat somatostatin sst2(a) and sst2(b) receptor isoforms mediate opposite effects on cell proliferation. Br. J. Pharmacol. 125, 1630-1633 (1998).
173. Ohki-Hamazaki, H., Iwabuchi, M. & Maekawa, F. Development and function of bombesin-like peptides and their receptors. Int. J. Dev. Biol. 49, 293-300 (2005).