Reg Proteins and Their Roles in Inflammation and Cancer of the Human Digestive System

Advances in Clinical Chemistry

Volumn 61, Issue , 2013, Pages 153-173

  Zhao, Jie ^a,b   Wang, Jingyu ^a   Wang, Hao ^a   Lai, Maode ^a  

^a ZHEJIANG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b ZHEJIANG SCI TECH UNIVERSITY   (China)

Author keywords

Cancer; Human digestive system; Inflammation; Reg gene; Reg1; Reg4

Indexed keywords

EID: 84878641062     PISSN: 00652423     EISSN: None     Source Type: Book Series    
DOI: 10.1016/B978-0-12-407680-8.00006-3     Document Type: Chapter

References (127)

1. Watanabe T., Yonekura H., Terazono K., Yamamoto H., Okamoto H. Complete nucleotide sequence of human reg gene and its expression in normal and tumoral tissues. The reg protein, pancreatic stone protein, and pancreatic thread protein are one and the same product of the gene. J. Biol. Chem. 1990, 265:7432-7439.
2. Terazono K., Yamamoto H., Takasawa S., et al. A novel gene activated in regenerating islets. J. Biol. Chem. 1988, 263:2111-2114.
3. Okamoto H. The Reg gene family and Reg proteins: with special attention to the regeneration of pancreatic beta-cells. J. Hepatobiliary Pancreat. Surg. 1999, 6:254-262.
4. Li F.Y., Ren X.B., Xu E.P., et al. Reg IV expression showing specificity to gastrointestinal tract and its potential role in diagnosing digestive tract neuroendocrine tumor. J. Zhejiang Univ. Sci. B 2010, 11:258-266.
5. Azman J., Starcevic Klasan G., Ivanac D., et al. Reg IV protein and mRNA expression in different rat organs. Acta Histochem. 2011, 113:793-797.
6. Starcevic-Klasan G., Azman J., Picard A., Jurisic-Erzen D., Nikolic M., Jerkovic R. Reg IV protein is expressed in normal rat tissue. Coll. Antropol. 2008, 32:89-93.
7. Hartupee J.C., Zhang H., Bonaldo M.F., Soares M.B., Dieckgraefe B.K. Isolation and characterization of a cDNA encoding a novel member of the human regenerating protein family: Reg IV. Biochim. Biophys. Acta 2001, 1518:287-293.
8. Satomura Y., Sawabu N., Ohta H., et al. The immunohistochemical evaluation of PSP/reg-protein in normal and diseased human pancreatic tissues. Int. J. Pancreatol. 1993, 13:59-67.
9. Okamoto H. Cyclic ADP-ribose-mediated insulin secretion and Reg, regenerating gene. J. Mol. Med. 1999, 77:74-78.
10. Unno M., Nata K., Noguchi N., et al. Production and characterization of Reg knockout mice: reduced proliferation of pancreatic beta-cells in Reg knockout mice. Diabetes 2002, 51:S478-S483.
11. Iovanna J.L., Dagorn J.C. The multifunctional family of secreted proteins containing a C-type lectin-like domain linked to a short N-terminal peptide. Biochim. Biophys. Acta 2005, 1723:8-18.
12. Drickamer K., Taylor M.E. Biology of animal lectins. Annu. Rev. Cell Biol. 1993, 9:237-264.
13. Ho M.R., Lou Y.C., Lin W.C., Lyu P.C., Chen C.P. Letter to the editor: H-1, C-13, and N-15 resonance assignments and secondary structure of human pancreatitis-associated protein (hPAP). J. Biomol. NMR 2004, 30:381-382.
14. Ho M.R., Lou Y.C., Wei S.Y., et al. Human Reg IV protein adopts a typical C-type lectin fold but binds mannan with two calcium-independent sites. J. Mol. Biol. 2010, 402:682-695.
15. Christa L., Felin M., Morali O., et al. The human HIP gene, overexpressed in primary liver cancer encodes for a C-type carbohydrate binding protein with lactose binding activity. FEBS Lett. 1994, 337:114-118.
16. Bernard-Perrone F.R., Renaud W.P., Guy-Crotte O.M., et al. Expression of REG protein during cell growth and differentiation of two human colon carcinoma cell lines. J. Histochem. Cytochem. 1999, 47:863-870.
17. Kobayashi S., Akiyama T., Nata K., et al. Identification of a receptor for Reg (Regenerating gene) protein, a pancreatic beta-cell regeneration factor. J. Biol. Chem. 2000, 275:10723-10726.
18. Kazumori H., Ishihara S., Fukuda R., Kinoshita Y. Localization of Reg receptor in rat fundic mucosa. J. Lab. Clin. Med. 2002, 139:101-108.
19. Bishnupuri K.S., Luo Q., Murmu N., Houchen C.W., Anant S., Dieckgraefe B.K. Reg IV activates the epidermal growth factor receptor/Akt/AP-1 signaling pathway in colon adenocarcinomas. Gastroenterology 2006, 130:137-149.
20. Bishnupuri K.S., Sainathan S.K., Luo Q., et al. T1172 Reg IV interacts with a cell-surface glycoprotein CD44 to induce mitotic division of human colorectal cancer cells. Gastroenterology 2010, 138:S504.
21. Watanabe T., Yonekura H., Terazono K., Yamamoto H., Okamoto H. Complete nucleotide sequence of human reg gene and its expression in normal and tumoral tissues. J. Biol. Chem. 1990, 265:7432-7439.
22. Chinuki D., Amano Y., Ishihara S., et al. REG I alpha protein expression in Barrett's esophagus. J. Gastroenterol. Hepatol. 2008, 23:296-302.
23. Rosty C., Christa L., Kuzdzal S., et al. Identification of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein I as a biomarker for pancreatic ductal adenocarcinoma by protein biochip technology. Cancer Res. 2002, 62:1868-1875.
24. Sekikawa A., Fukui H., Fujii S., et al. REG I alpha protein may function as a trophic and/or anti-apoptotic factor in the development of gastric cancer. Gastroenterology 2005, 128:642-653.
25. Lasserre C., Christa L., Simon M.T., Vernier P., Brechot C. A novel gene (HIP) activated in human primary liver cancer. Cancer Res. 1992, 52:5089-5095.
26. Oue N., Mitani Y., Aung P.P., et al. Expression and localization of Reg IV in human neoplastic and non-neoplastic tissues: Reg IV expression is associated with intestinal and neuroendocrine differentiation in gastric adenocarcinoma. J. Pathol. 2005, 207:185-198.
27. Zheng H.C., Xu X.Y., Yu M., Takahashi H., Masuda S., Takano Y. The role of Reg IV gene and its encoding product in gastric carcinogenesis. Hum. Pathol. 2010, 41:59-69.
28. Sentani K., Oue N., Tashiro T., et al. Immunohistochemical staining of Reg IV and claudin-18 is useful in the diagnosis of gastrointestinal signet ring cell carcinoma. Am. J. Surg. Pathol. 2008, 32:1182-1189.
29. Azman J., Starcevic Klasan G., Ivanac D., et al. Reg IV protein and mRNA expression in different rat organs. Acta Histochem. 2010, 113:793-797.
30. Parikh A., Stephan A.F., Tzanakakis E.S. Regenerating proteins and their expression, regulation and signaling. Biomol. Concepts 2012, 3:57-70.
31. Akiyama T., Takasawa S., Nata K., et al. Activation of Reg gene, a gene for insulin-producing beta-cell regeneration: poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by autopoly(ADP-ribosyl)ation. Proc. Natl. Acad. Sci. U.S.A. 2001, 98:48-53.
32. Dusetti N.J., Mallo G.V., Ortiz E.M., Keim V., Dagorn J.C., Iovanna J.L. Induction of lithostathine/reg mRNA expression by serum from rats with acute pancreatitis and cytokines in pancreatic acinar AR-42J cells. Arch. Biochem. Biophys. 1996, 330:129-132.
33. Kazumori H., Ishihara S., Hoshino E., et al. Neutrophil chemoattractant 2 beta regulates expression of the Reg gene in injured gastric mucosa in rats. Gastroenterology 2000, 119:1610-1622.
34. Kinoshita Y., Ishihara S., Kadowaki Y., Fukui H., Chiba T. Reg protein is a unique growth factor of gastric mucosal cells. J. Gastroenterol. 2004, 39:507-513.
35. Yoshino N., Ishihara S., Rumi M.A., et al. Interleukin-8 regulates expression of Reg protein in Helicobacter pylori-infected gastric mucosa. Am. J. Gastroenterol. 2005, 100:2157-2166.
36. Sekikawa A., Fukui H., Fujii S., et al. Possible role of REG I alpha protein in ulcerative colitis and colitic cancer. Gut 2005, 54:1437-1444.
37. Sekikawa A., Fukui H., Fujii S., et al. REG I alpha protein mediates an anti-apoptotic effect of STAT3 signaling in gastric cancer cells. Carcinogenesis 2008, 29:76-83.
38. Nanakin A., Fukui H., Fujii S., et al. Expression of the REG IV gene in ulcerative colitis. Lab. Invest. 2007, 87:304-314.
39. Moucadel V., Soubeyran P., Vasseur S., Dusetti N.J., Dagorn J.C., Iovanna J.L. Cdx1 promotes cellular growth of epithelial intestinal cells through induction of the secretory protein PAP I. Eur. J. Cell Biol. 2001, 80:156-163.
40. Wang F., Xu L., Guo C.Y., et al. Identification of Reg IV as a novel GLI1 target gene in human pancreatic cancer. PLoS One 2011, 6:e18434.
41. Buendia M.A. Genetics of hepatocellular carcinoma. Semin. Cancer Biol. 2000, 10:185-200.
42. Cavard C., Terris B., Grimber G., et al. Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with beta-catenin mutations. Oncogene 2006, 25:599-608.
43. Coussens L.M., Werb Z. Inflammation and cancer. Nature 2002, 420:860-867.
44. Weis W.I., Kahn R., Fourme R., Drickamer K., Hendrickson W.A. Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing. Science 1991, 254:1608-1615.
45. Kishore U., Eggleton P., Reid K.B.M. Modular organization of carbohydrate recognition domains in animal lectins. Matrix Biol. 1997, 15:583-592.
46. Zhang Y.W., Lai M.D., Lv B.J., et al. Overexpression of Reg IV in colorectal adenoma. Cancer Lett. 2003, 200:69-76.
47. Usami S., Motoyama S., Koyota S., et al. Regenerating gene I regulates interleukin-6 production in squamous esophageal cancer cells. Biochem. Biophys. Res. Commun. 2010, 392:4-8.
48. Oue N., Noguchi T., Anami K., et al. Serum concentration and expression of Reg IV in patients with esophageal cancer: age-related elevation of serum Reg IV concentration. Oncol. Lett. 2011, 2:235-239.
49. Kleinberg L., Forastiere A.A. Chemoradiation in the management of esophageal cancer. J. Clin. Oncol. 2007, 25:4110-4117.
50. Coia L.R. Chemoradiation as primary management of esophageal cancer. Semin. Oncol. 1994, 21:483-492.
51. Shimoyama S., Aoki F., Murakami T., Toyoda K., Kaminishi M. Feasibility of daily concurrent chemoradiation therapy as nonsurgical management for esophageal cancer: our experience and theoretical background. J. Surg. Oncol. 2000, 74:134-137.
52. Motoyama S., Sugiyama T., Ueno Y., et al. REG I expression predicts long-term survival among locally advanced thoracic squamous cell esophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by esophagectomy. Ann. Surg. Oncol. 2006, 13:1724-1731.
53. Hayashi K., Motoyama S., Koyota S., et al. REG I enhances chemo- and radiosensitivity in squamous cell esophageal cancer cells. Cancer Sci. 2008, 99:2491-2495.
54. Hayashi K., Motoyama S., Sugiyama T., et al. REG I alpha is a reliable marker of chemoradiosensitivity in squamous cell esophageal cancer patients. Ann. Surg. Oncol. 2008, 15:1224-1231.
55. Fukui H., Sekikawa A., Chiba T. REG (regenerating gene) protein-roles of REG protein in H. pylori-induced gastritis and gastric cancers. Nihon. Rinsho. 2005, 63:98-102.
56. Fukui H., Franceschi F., Penland R.L., et al. Effects of Helicobacter pylori infection on the link between regenerating gene expression and serum gastrin levels in Mongolian gerbils. Lab. Invest. 2003, 83:1777-1786.
57. Yonemura Y., Sakurai S., Yamamoto H., et al. REG gene expression is associated with the infiltrating growth of gastric carcinoma. Cancer 2003, 98:1394-1400.
58. Yamagishi H., Fukui H., Sekikawa A., et al. Expression profile of REG family proteins REG I alpha and REG IV in advanced gastric cancer: comparison with mucin phenotype and prognostic markers. Mod. Pathol. 2009, 22:906-913.
59. Sentani K., Oue N., Noguchi T., Sakamoto N., Matsusaki K., Yasui W. Immunostaining of gastric cancer with neuroendocrine differentiation: Reg IV-positive neuroendocrine cells are associated with gastrin, serotonin, pancreatic polypeptide and somatostatin. Pathol. Int. 2010, 60:291-297.
60. Yasui W., Oue N., Ito R., Kuraoka K., Nakayama H. Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implications. Cancer Sci. 2004, 95:385-392.
61. Suh Y.S., Lee H.J., Jung E.J., et al. The combined expression of metaplasia biomarkers predicts the prognosis of gastric cancer. Ann. Surg. Oncol. 2011, 19:1240-1249.
62. Mitani Y., Oue N., Matsumura S., et al. Reg IV is a serum biomarker for gastric cancer patients and predicts response to 5-fluorouracil-based chemotherapy. Oncogene 2007, 26:4383-4393.
63. Oue N., Sentani K., Noguchi T., et al. Serum olfactomedin 4 (GWI 12, hGC4) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients. Int. J. Cancer 2009, 125:2383-2392.
64. Dhar D.K., Udagawa J., Ishihara S., et al. Expression of regenerating gene I in gastric adenocarcinomas-correlation with tumor differentiation status and patient survival. Cancer 2004, 100:1130-1136.
65. Fukui H., Fujii S., Takeda J., et al. Expression of reg I alpha protein in human gastric cancers. Digestion 2004, 69:177-184.
66. Miyagawa K., Sakakura C., Kin S., et al. Over expression of Reg IV in peritoneal dissemination of gastric cancer. Gan To Kagaku Ryoho 2004, 31:1909-1911.
67. Kuniyasu H., Oue N., Sasahira T., et al. Reg IV enhances peritoneal metastasis in gastric carcinomas. Cell Prolif. 2009, 42:110-121.
68. Moon J.H., Fujiwara Y., Nakamura Y., et al. REGIV as a potential biomarker for peritoneal dissemination in gastric adenocarcinoma. J. Surg. Oncol. 2012, 105:189-194.
69. Granlund A.B., Beisvag V., Torp S.H., et al. Activation of REG family proteins in colitis. Scand. J. Gastroenterol. 2011, 46:1316-1323.
70. Fukui H., Sekikawa A., Fujimori T., Chiba T. Expression of REG IV gene in ulcerative colitis and colitic cancer. Regul. Peptides 2006, 135:125.
71. Glebov O.K., Rodriguez L.M., Soballe P., et al. Gene expression patterns distinguish colonoscopically isolated human aberrant crypt foci from normal colonic mucosa. Cancer Epidemiol. Biomarkers Prev. 2006, 15:2253-2262.
72. Zheng H.C., Sugawara A., Okamoto H., et al. Expression profile of the REG gene family in colorectal carcinoma. J. Histochem. Cytochem. 2011, 59:106-115.
73. Yeh C.S., Wang J.Y., Wu C.H., et al. Molecular detection of circulating cancer cells in the peripheral blood of patients with colorectal cancer by using membrane array with a multiple mRNA marker panel. Int. J. Oncol. 2006, 28:411-420.
74. Pankova-Kholmyansky I., Arber N. Reg IV can serve for early diagnosis and therapy. Cancer Biol. Ther. 2007, 6:123-124.
75. Violette S., Festor E., Pandrea-Vasile I., et al. Reg IV, a new member of the regenerating gene family, is overexpressed in colorectal carcinomas. Int. J. Cancer 2003, 103:185-193.
76. Numata M., Oshima T., Yoshihara K., et al. Relationship between RegIV gene expression to outcomes in colorectal cancer. J. Surg. Oncol. 2011, 104:205-209.
77. Rafa L., Dessein A.F., Devisme L., et al. REG4 acts as a mitogenic, motility and pro-invasive factor for colon cancer cells. Int. J. Oncol. 2010, 36:689-698.
78. Guo Y., Xu J.J., Li N., Gao F., Huang P.L. RegIV potentiates colorectal carcinoma cell migration and invasion via its CRD domain. Cancer Genet. Cytogenet. 2010, 199:38-44.
79. Oue N., Hamai Y., Mitani Y., et al. Gene expression profile of gastric carcinoma: identification of genes and tags potentially involved in invasion, metastasis, and carcinogenesis by serial analysis of gene expression. Cancer Res. 2004, 64:2397-2405.
80. Roeb E., Matern S. Matrix metalloproteinases and colorectal cancer. Med. Klin. (Munich) 2003, 98:763-770.
81. Oue N., Kuniyasu H., Noguchi T., et al. Serum concentration of Reg IV in patients with colorectal cancer: overexpression and high serum levels of Reg IV are associated with liver metastasis. Oncology (Basel) 2007, 72:371-380.
82. Vanderlaag K., Wang W., Fayadat-Dilman L., et al. Regenerating islet-derived family member, 4 modulates multiple receptor tyrosine kinases and mediators of drug resistance in cancer. Int. J. Cancer 2012, 130:1251-1263.
83. Bishnupuri K.S., Luo Q.Z., Sainathan S.K., et al. Reg IV regulates normal intestinal and colorectal cancer cell susceptibility to radiation-induced apoptosis. Gastroenterology 2010, 138:616-626.
84. Kobunai T., Watanabe T., Fukusato T. REG4, NEIL2, and BIRC5 gene expression correlates with gamma-radiation sensitivity in patients with rectal cancer receiving radiotherapy. Anticancer Res. 2011, 31:4147-4153.
85. Luo Q., Bishnupuri K.S., Houchen C., Anant S., Dieckgraefe B.K. Silencing of the regenerating IV (Reg IV) gene by siRNA inhibits the growth and proliferation of human colon adenocarcinomas. Gastroenterology 2006, 130:A533.
86. Luo Q., Bishnupuri K.S., Houchen C.W., Anant S., Dieckgraefe B.K. Specific monoclonal antibodies directed against reg IV protein inhibits cell proliferation and induces apoptotic death of human colon adenocarcinomas. Gastroenterology 2007, 132:A426.
87. Li Y.G., Ji D.F., Zhong S., Zhu J.X., Chen S., Hu G.Y. Anti-tumor effects of proteoglycan from Phellinus linteus by immunomodulating and inhibiting Reg IV/EGFR/Akt signaling pathway in colorectal carcinoma. Int. J. Biol. Macromol. 2011, 48:511-517.
88. Mayer J., Rau B., Gansauge F., Beger H.G. Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications. Gut 2000, 47:546-552.
89. Toma H., Winston J., Micci M.A., Shenoy M., Pasricha P.J. Nerve growth factor expression is up-regulated in the rat model of L-arginine-induced acute pancreatitis. Gastroenterology 2000, 119:1373-1381.
90. Norman J. The role of cytokines in the pathogenesis of acute pancreatitis. Am. J. Surg. 1998, 175:76-83.
91. Dawra R., Sharif R., Phillips P., Dudeja V., Dhaulakhandi D., Saluja A.K. Development of a new mouse model of acute pancreatitis induced by administration of L-arginine. Am. J. Physiol. Gastroint. Liver Physiol. 2007, 292:G1009-G1018.
92. Adler G., Hahn C., Kern H.F., Rao K.N. Cerulein-induced pancreatitis in rats: increased lysosomal enzyme activity and autophagocytosis. Digestion 1985, 32:10-18.
93. Keim V., Iovanna J.L., Rohr G., Usadel K.H., Dagorn J.C. Characterization of a rat pancreatic secretory protein associated with pancreatitis. Gastroenterology 1991, 100:775-782.
94. Tezel E., Nagasaka T., Tezel G., et al. REG I as a marker for human pancreatic acinoductular cells. Hepatogastroenterology 2004, 51:91-96.
95. Bluth M.H., Patel S.A., Dieckgraefe B.K., Okamoto H., Zenilman M.E. Pancreatic regenerating protein (reg I) and reg I receptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis. World J. Gastroenterol. 2006, 12:4511-4516.
96. Orelle B., Keim V., Masciotra L., Dagorn J.C., Iovanna J.L. Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases. J. Clin. Invest. 1992, 90:2284-2291.
97. Ortiz E.M., Dusetti N.J., Vasseur S., et al. The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis. Gastroenterology 1998, 114:808-816.
98. Gironella M., Iovanna J.L., Sans M., et al. Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease. Gut 2005, 54:1244-1253.
99. Lin Y.Y., Viterbo D., Mueller C.M., et al. Small-interference RNA gene knockdown of pancreatitis-associated proteins in rat acute pancreatitis. Pancreas 2008, 36:402-410.
100. Gironella M., Folch-Puy E., LeGoffic A., et al. Experimental acute pancreatitis in PAP/HIP knock-out mice. Gut 2007, 56:1091-1097.
101. Zenilman M.E., Tuchman D., Zheng Q., Levine J., Delany H. Comparison of reg I and reg III levels during acute pancreatitis in the rat. Ann. Surg. 2000, 232:646-652.
102. Takayama R., Nakagawa H., Sawaki A., et al. Serum tumor antigen REG4 as a diagnostic biomarker in pancreatic ductal adenocarcinoma. J. Gastroenterol. 2010, 45:52-59.
103. Legoffic A., Calvo E., Cano C., et al. The reg4 gene, amplified in the early stages of pancreatic cancer development, is a promising therapeutic target. PLoS One 2009, 4:e7495.
104. Dembinski A., Warzecha Z., Konturek P.C., et al. Epidermal growth factor accelerates pancreatic recovery after caerulein-induced pancreatitis. Eur. J. Pharmacol. 2000, 398:159-168.
105. Hu G., Shen J., Cheng L., et al. Reg4 protects against acinar cell necrosis in experimental pancreatitis. Gut 2011, 60:820-828.
106. Warzecha Z., Dembinski A., Konturek P.C., Ceranowicz P., Konturek S.J. Epidermal growth factor protects against pancreatic damage in cerulein-induced pancreatitis. Digestion 1999, 60:314-323.
107. Zhou L., Zhang R., Wang L., et al. Upregulation of REG Ialpha accelerates tumor progression in pancreatic cancer with diabetes. Int. J. Cancer 2010, 127:1795-1803.
108. Takehara A., Eguchi H., Ohigashi H., et al. Novel tumor marker REG4 detected in serum of patients with resectable pancreatic cancer and feasibility for antibody therapy targeting REG4. Cancer Sci. 2006, 97:1191-1197.
109. Nakata K., Nagai E., Ohuchida K., et al. REG4 is associated with carcinogenesis in the 'intestinal' pathway of intraductal papillary mucinous neoplasms. Mod. Pathol. 2009, 22:460-468.
110. Motoo Y., Satomura Y., Mouri I., et al. Serum levels of pancreatitis-associated protein in digestive diseases with special reference to gastrointestinal cancers. Dig. Dis. Sci. 1999, 44:1142-1147.
111. Sawaki A., Takayama R., Mizuno N., et al. A prospective study for serum REG4 protein in pancreatic cancer as a tumor marker. Eur. J. Cancer 2007, 5:S277-S278.
112. Eguchi H., Ishikawa O., Ohigashi H., et al. Serum REG4 level is a predictive biomarker for the response to preoperative chemoradiotherapy in patients with pancreatic cancer. Pancreas 2009, 38:791-798.
113. Christa L., Simon M.T., Brezault-Bonnet C., et al. Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) is expressed and secreted by proliferating ductules as well as by hepatocarcinoma and cholangiocarcinoma cells. Am. J. Pathol. 1999, 155:1525-1533.
114. Harada K., Zen Y., Kanemori Y., et al. Human REG I gene is up-regulated in intrahepatic cholangiocarcinoma and its precursor lesions. Hepatology 2001, 33:1036-1042.
115. Lieu H.T., Batteux F., Simon M.T., et al. HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice. Hepatology 2005, 42:618-626.
116. Yang L., Lan S., Liu J., Yang Z. Expression of MK-1 and RegIV and its clinicopathological significances in the benign and malignant lesions of gallbladder. Diagn. Pathol. 2011, 6:100.
117. Liu B.K., Herve J., Bioulac-Sage P., et al. Sodium iodide symporter is expressed at the preneoplastic stages of liver carcinogenesis and in human cholangiocarcinoma. Gastroenterology 2007, 132:1495-1503.
118. Filetti S., Bidart J.M., Arturi F., Caillou B., Russo D., Schlumberger M. Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism. Eur. J. Endocrinol. 1999, 141:443-457.
119. Herve J., Cunha A.S., Liu B., et al. Internal radiotherapy of liver cancer with rat hepatocarcinoma-intestine-pancreas gene as a liver tumor-specific promoter. Hum. Gene Ther. 2008, 19:915-926.
120. Mueller C.M., Zhang H., Zenilman M.E. Pancreatic reg I binds MKP-1 and regulates cyclin D in pancreatic-derived cells. J. Surg. Res. 2008, 150:137-143.
121. Takasawa S., Ikeda T., Akiyama T., et al. Cyclin D1 activation through ATF-2 in Reg-induced pancreatic beta-cell regeneration. FEBS Lett. 2006, 580:585-591.
122. Simon M.T., Pauloin A., Normand G., et al. HIP/PAP stimulates liver regeneration after partial hepatectomy and combines mitogenic and anti-apoptotic functions through the PKA signaling pathway. FASEB J. 2003, 17:1441-1450.
123. Demaugre F., Philippe Y., Sar S., et al. HIP/PAP, a C-type lectin overexpressed in hepatocellular carcinoma, binds the RII alpha regulatory subunit of cAMP-dependent protein kinase and alters the cAMP-dependent protein kinase signalling. Eur. J. Biochem. 2004, 271:3812-3820.
124. Lieu H.T., Simon M.T., Nguyen-Khoa T., et al. Reg2 inactivation increases sensitivity to Fas hepatotoxicity and delays liver regeneration post-hepatectomy in mice. Hepatology 2006, 44:1452-1464.
125. Kadowaki T., Ueki K., Yamauchi T., Kubota N. SnapShot: insulin signaling pathways. Cell 2012, 148:624. 624.e621.
126. Ziske C., Marten A., Schottker B., et al. Resistance of pancreatic carcinoma cells is reversed by coculturing NK-like T cells with dendritic cells pulsed with tumor-derived RNA and CA 19-9. Mol. Ther. 2001, 3:54-60.
127. Karin M., Greten F.R. NF kappa B: linking inflammation and immunity to cancer development and progression. Nat. Rev. Immunol. 2005, 5:749-759.