Pancreatic stone protein/regenerating protein family in pancreatic and gastrointestinal diseases

Internal Medicine

Volumn 50, Issue 15, 2011, Pages 1507-1516

  Jin, Chun Xiang ^a   Hayakawa, Tetsuo ^b   Ko, Shigeru B H ^c   Ishiguro, Hiroshi ^c   Kitagawa, Motoji ^d  

^a JILIN UNIVERSITY   (China)

^b Meijo Hospital   (Japan)

^c NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^d NAGOYA UNIVERSITY OF ARTS AND SCIENCES   (Japan)

Author keywords

Lithostathine; Pancreatic and GI diseases; Pancreatic stone protein; Pancreatitis associated protein; Regenerating protein

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ALBUMIN; ANTINEOPLASTIC AGENT; C REACTIVE PROTEIN; CALCIUM CARBONATE; LITHOSTATHINE; PANCREATITIS ASSOCIATED PROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; TRYPSIN; TRYPSINOGEN;

ACUTE PANCREATITIS; ANTIINFLAMMATORY ACTIVITY; BILE DUCT CARCINOMA; CANCER SURVIVAL; CHRONIC PANCREATITIS; COLORECTAL CANCER; DIABETES MELLITUS; ESOPHAGEAL SQUAMOUS CELL CARCINOMA; GASTROINTESTINAL DISEASE; HUMAN; LIVER CELL CARCINOMA; MITOGENESIS; NONHUMAN; OCCLUSION; PANCREAS CANCER; PANCREAS DISEASE; PANCREAS ISLET; PANCREAS JUICE; PANCREAS STONE; PANCREATIC STENT; PROGNOSIS; REGENERATION; REVIEW; SENSITIVITY AND SPECIFICITY; STENT; STENT OCCLUSION; STOMACH CANCER; STONE FORMATION;

ANIMALS; ANTIGENS, NEOPLASM; BACTERIAL PHYSIOLOGICAL PHENOMENA; CALCULI; DIABETES MELLITUS; GASTROINTESTINAL DISEASES; HUMANS; ISLETS OF LANGERHANS; LECTINS, C-TYPE; LITHOSTATHINE; MITOSIS; NEOPLASMS; PANCREATIC DISEASES; PANCREATITIS, CHRONIC; PROGNOSIS; REGENERATION; TUMOR MARKERS, BIOLOGICAL;

EID: 79961198265     PISSN: 09182918     EISSN: 13497235     Source Type: Journal    
DOI: 10.2169/internalmedicine.50.5362     Document Type: Review

References (136)

1. De Caro A, Lohse J, Sarles H. Characterization of a protein isolated from pancreatic calculi of men suffering from chronic calcifying pancreatitis. Biochem Biophys Res Commun 87: 1176-1182, 1979.
2. Gross J, Brauer AW, Bringhurst RF, Corbett C, Margolies MN. An unusual bovine pancreatic protein exhibiting pH-dependent globule-fibril transformation and unique amino acid sequence. Proc Natl Acad Sci USA 82: 5627-5631, 1985.
3. Gross J, Carlson RI, Brauer AW, Margolies MN, Warshaw AL, Wands JR. Isolation, characterization, and distribution of an unusual pancreatic human secretory protein. J Clin Invest 76: 2115-2126, 1985.
4. Terazono K, Yamamoto H, Takasawa S, et al. A novel gene activated in regenerating islets. J Biol Chem 263: 2111-2114, 1988.
5. Keim V, Rohr G, Söckert HG, Haberich FJ. An additional secretory protein in the rat pancreas. Digestion 29: 242-249, 1984.
6. Keim V, Iovanna JL, Orelle B, et al. A novel exocrine protein associated with pancreas transplantation in human. Gastroenterology 103: 248-254, 1992.
7. Graf R, Schiesser M, Scheele GA, et al. A family of 16-kDa pancreatic secretory stress proteins form highly organized fibrillar structures upon tryptic activation. J Biol Chem 276: 21028-21038, 2001.
8. Hayakawa T, Naruse S, Kitagawa M, Nakae Y, Hayakawa S. Current status of pancreatic stone protein. Nagoya J Med Sci 57: 109-118, 1994.
9. Graf R, Schiesser M, Reding T, et al. Exocrine meets endocrine: pancreatic stone protein and regenerating protein--two sides of the same coin. J Surg Res 133: 113-120, 2006.
10. de Reggi M, Gharib B. Protein-X, Pancreatic Stone-, Pancreatic thread-, reg-protein, P19, lithostathine, and now what? Characterization, structural analysis and putative function(s) of the major non-enzymatic protein of pancreatic secretions. Curr Protein Pept Sci 2: 19-42, 2001.
11. Zhang YW, Ding LS, Lai MD. Reg gene family and human diseases. World J Gastroenterol 9: 2635-2641, 2003.
12. Patard L, Lallemand JY, Stoven V. An insight into the role of human pancreatic lithostathine. JOP 4: 92-103, 2003.
13. de Caro A, Multigner L, Lafont H, Lombardo D, Sarles H. The molecular characteristics of a human pancreatic acidic phospho-protein that inhibits calcium carbonate crystal growth. Biochem J 222: 669-677, 1984.
14. Multigner L, de Caro A, Lombardo D, Campese D, Sarles H. Pancreatic stone protein, a phosphoprotein which inhibits calcium carbonate precipitation from human pancreatic juice. Biochem Biophys Res Commun 110: 69-74, 1983.
15. Montalto G, Bonicel J, Multigner L, Rovery M, Sarles H, de Caro A. Partial amino acid sequence of human pancreatic stone protein, a novel pancreatic secretory protein. Biochem J 238: 227-232, 1986.
16. de Caro AM, Bonicel JJ, Rouimi P, De Caro JD, Sarles H, Rov-ery M. Complete amino acid sequence of an immunoreactive form of human pancreatic stone protein isolated from pancreatic juice. Eur J Biochem 168: 201-207, 1987.
17. de Caro A, Multigner L, Dagorn JC, Sarles H. The human pancreatic stone protein. Biochimie 70: 1209-1214, 1988.
18. de Caro AM, Adrich Z, Fournet B, et al. N-terminal sequence extension in the glycosylated forms of human pancreatic stone protein. The 5-oxoproline N-terminal chain is O-glycosylated on the 5th amino acid residue. Biochim Biophys Acta 994: 281-284, 1989.
19. Rouimi P, Bonicel J, Rovery M, de Caro A. Cleavage of the Arg-Ile bond in the native polypeptide chain of human pancreatic stone protein. FEBS Lett 216: 195-199, 1987.
20. Giorgi D, Bernard JP, Rouquier S, Iovanna J, Sarles H, Dagorn JC. Secretory pancreatic stone protein messenger RNA. Nucleotide sequence and expression in chronic calcifying pancreatitis. J Clin Invest 84: 100-106, 1989.
21. de Reggi M, Capon C, Gharib B, Wieruszeski JM, Michel R, Fournet B. The glycan moiety of human pancreatic lithostathine. Structure characterization and possible pathophysiological implications. Eur J Biochem 230: 503-510, 1995.
22. Kato M, Hayakawa S, Naruse S, et al. Change of pancreatic enzymes, pancreatic stone protein (PSP), and plasma α2-macroglobulin-trypsin complex-like substance (MTLS) in the activation of pancreatic juice. Pancreas 15: 345-349, 1997.
23. Cerini C, Peyrot V, Garnier C, et al. Biophysical characterization of lithostathine. Evidences for a polymeric structure at physiological pH and a proteolysis mechanism leading to the formation of fibrils. J Biol Chem 274: 22266-22274, 1999.
24. Schiesser M, Bimmler D, Frick TW, Graf R. Conformational changes of pancreatitis-associated protein (PAP) activated by tryp-sin lead to insoluble protein aggregates. Pancreas 22: 186-192, 2001.
25. 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 265: 7432-7439, 1990.
26. Unno M, Yonekura H, Nakagawara K, et al. Structure, chromosomal localization, and expression of mouse reg genes, reg I and reg II. A novel type of reg gene, reg II, exists in the mouse genome. J Biol Chem 268: 15974-15982, 1993.
27. Stewart TA. The human reg gene encodes pancreatic stone protein. Biochem J 260: 622-623, 1989.
28. Rouquier S, Giorgi S, Iovanna J, Dagorn JC. Sequence similarity between the reg transcript and pancreatic stone protein mRNA. Biochem J 264: 621-622, 1989.
29. Closa D, Motoo Y, Iovanna JL. Pancreatitis-associated protein: from a lectin to an anti-inflammatory cytokine. World J Gastroen-terol 13: 170-174, 2007.
30. Iovanna J, Orelle B, Keim V, Dagorn JC. Messenger RNA sequence and expression of rat pancreatitis-associated protein, a lectin-related protein overexpressed during acute experimental pancreatitis. J Biol Chem 266: 24664-24669, 1991.
31. Sarles H. Etiopathogenesis and definition of chronic pancreatitis. Dig Dis Sci 31: 91s-107s, 1986.
32. Sarles H, Dagorn JC, Giorgi D, Bernard JP. Renaming pancreatic stone protein as 'lithostathine'. Gastroenterology 99: 900-901, 1990.
33. Bernard JP, Adrich Z, Montalto G, et al. Inhibition of nucleation and crystal growth of calcium carbonate by human lithostathine. Gastroenterology 103: 1277-1284, 1992.
34. Geider S, Baronnet A, Cerini C, et al. Pancreatic lithostathine as a calcite habit modifier. J Biol Chem 271: 26302-26306, 1996.
35. Multigner L, Sarles H, Lombardo D, de Caro A. Pancreatic stone protein. II. Implication in stone formation during the course of chronic calcifying pancreatitis. Gastroenterology 89: 387-391, 1985.
36. Provansal-Cheylan M, Mariani A, Bernard JP, Sarles H, Dupuy P. Pancreatic stone protein: quantification in pancreatic juice by enzyme-linked immunosorbent assay and comparison with other methods. Pancreas 4: 680-689, 1989.
37. Yamadera K, Wada K, Goto M, et al. Quantification of human lithostathine S2-5 forms using the antibody to the N-terminal pep-tide region. Pancreas 16: 475-480, 1998.
38. Mariani A, Mezzi G, Malesci A. Purification and assay of secretory lithostathine in human pancreatic juice by fast protein liquid chromatography. Gut 36: 622-629, 1995.
39. Schmiegel W, Burchert M, Kalthoff H, et al. Immunochemical characterization and quantitative distribution of pancreatic stone protein in sera and pancreatic secretions in pancreatic disorders. Gastroenterology 99: 1421-1430, 1990.
40. Hayakawa T, Naruse S, Kitagawa M, et al. Pancreatic stone protein and lactoferrin in human pancreatic juice in chronic pancreatitis. Pancreas 10: 137-142, 1995.
41. Renner IG, Rinderknecht H, Douglas AP. Profiles of pure pancreatic secretions in patients with acute pancreatitis: the possible role of proteolytic enzymes in pathogenesis. Gestroenterology 75: 1090-1098, 1978.
42. Geokas MC, Rinderknecht H. Free proteolytic enzymes in pancreatic juice of patients with acute pancreatitis. Am J Dig Dis 19: 591-598, 1974.
43. Bimmler D, Graf R, Scheele GA, Frick TW. Pancreatic stone protein (lithostathine), a physiologically relevant pancreatic calcium carbonate crystal inhibitor? J Biol Chem 272: 3073-3082, 1997.
44. Bimmler D, Graf R, Frick T. Human lithostathine S2-5: a relevant inhibitor of pancreatic stone formation? Pancreas 18: 417-418, 1999.
45. De Reggi M, Gharib B, Patard L, Stoven V. Lithostathine, the presumed pancreatic stone inhibitor, does not interact specifically with calcium carbonate crystals. J Biol Chem 273: 4967-4971, 1998.
46. Guy O, Robles-Diaz G, Adrich Z, Sahel J, Sarles H. Protein content of precipitates present in pancreatic juice of alcoholic subjects and patients with chronic calcifying pancreatitis. Gastrotenterology 84: 102-107, 1983.
47. Katsuzaki T, Tatemichi N, Takeichi C, et al. Enzyme immunoas-say for specific analysis of pancreatic stone proteins in human pancreatic juice. J Clin Lab Anal 6: 375-378, 1992.
48. Montalto G, Multigner L, Sarles H, de Caro A. Organic matrix of pancreatic stones associated with nutritional pancreatitis. Pancreas 3: 263-268, 1988.
49. Bockman DE, Kennedy RH, Multigner L, de Caro A, Sarles H. Fine structure of the organ matrix of human pancreatic stones. Pancreas 1: 204-210, 1986.
50. Yamadera K, Moriyama T, Makino I. Identification of immunore-active pancreatic stone protein in pancreatic stone, pancreatic tissue and pancreatic juice. Pancreas 5: 255-260, 1990.
51. Jin CX, Naruse S, Kitagawa M, et al. Pancreatic stone protein of pancreatic calculi in chronic calcified pancreatitis in man. JOP 3: 54-61, 2002.
52. Mariani A, Bernard JP, Provansal-Cheylan M, Nitsche S, Sarles H. Differences of pancreatic stone morphology and content in patients with pancreatic lithiasis. Dig Dis Sci 36: 1509-1516, 1991.
53. Harada H, Takeda M, Tanaka J, Miki H, Ochi K, Kimura I. The fine structure of pancreatic stones as shown by scanning electron microscopy and X-ray probe microanalyser. Gastroenterol Jpn 18: 530-537, 1983.
54. Hayakawa T, Kondo T, Shibata T, Kitagawa M, Nakae Y, Haya-kawa S. Trypsin(ogen) content of pancreatic calculi in chronic calcified pancreatitis in man. Dig Dis Sci 39: 1345-1350, 1994.
55. Kitagawa M, Hayakawa T, Kondo T, et al. Pancreatic stone predominantly composed of fatty acid calcium. Gastroenterology 102: 2151-2154, 1992.
56. Pithchumoni CS, Viswanthan KV, Gee Varghese PJ, Banks PA. Ultrastructure and elemental composition of human pancreatic calculi. Pancreas 2: 152-158, 1987.
57. Provansal-Cheylan M, Bernard JP, Mariani A, et al. Occluded pancreatic endoprostheses-analysis of the clogging material. Endo-scopy 21: 63-69, 1989.
58. Smits ME, Groen AK, Mok KS, van Marie J, Tytgat GN, Hui-bregtse K. Analysis of occuluded pancreatic stents in patients with chronic pancreatitis. Gastrointest Endosc 45: 52-58, 1997.
59. Farnbacher MJ, Voll RE, Faissner R, et al. Composition of clogging material in pancreatic endoprostheses. Gastrointest Endosc 61: 862-866, 2005.
60. Buscaglia JM, DiMaio CJ, Pollack MJ, et al. Are large side holes associated with reduced rates of pancreatic stent occlusion? Results of a prospective study. JOP 10: 496-500, 2009.
61. Iovanna J, Frigerio JM, Dusetti N, Ramare F, Raibaud P, Dagorn JC. Lithostathine, an inhibitor of CaCO3 crystal growth in pancreatic juice, induces bacterial aggregation. Pancreas 8: 597-601, 1993.
62. Medveczky P, Szmola R, Sahin-Tóth M. Proteolytic activation of human pancreatitis-associated protein is required for peptidoglycan binding and bacterial aggregation. Biochem J 420: 335-343, 2009.
63. Mukherjee S, Parteh CL, Lehotzky RE, et al. Regulation of C-type lectin antimicrobial activity by a flexible N-terminal proseg-ment. J Biol Chem 284: 4881-4888, 2009.
64. Harada H, Ueda O, Yasuoka M, et al. Histochemical studies on protein plugs obtained by endoscopic retrograde catheterization of the papilla. Gastroenterol Jpn 16: 563-567, 1981.
65. Marotta F, Tajiri H, Li ZL, Barreto R, Bellini O, Barbi G. Pure pancreatic juice from patients with chronic pancreatitis has an impaired antibacterial activity. Int J Pancreatol 22: 215-220, 1997.
66. Cash HL, Whitham CV, Behrendt CL, Hooper LV. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313: 1126-1130, 2006.
67. Orelle B, Keim V, Masciotra L, Dagorn JC, Iovanna JL. Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases. J Clin Invest 90: 2284-2291, 1992.
68. Iovanna JL, Keim V, Nordback I, et al. Serum levels of pancreatitis-associated protein as indicators of the course of acute pancreatitis. Multicentric Study Group on Acute Pancreatitis. Gas-troenterology 106: 728-734, 1994.
69. Pezzilli R, Billi P, Migliori M, Gullo L. Clinical value of pancreatitis-associated protein in acute pancreatitis. Am J Gastro-enterol 92: 1887-1890, 1997.
70. Polanec J, Pavelic ZP, Krizman I, Osredkar J. Low serum pancreatitis-associated protein does not exclude complications in mild acute pancreatitis. Pathol Oncol Res 3: 30-33, 1997.
71. Duarte-Rojo A, Suazo-Barahona J, Ramírez-Iglesias MT, Uscanga LF, Robles-Díaz G. Time frames for analysis of inflammatory mediators in acute pancreatitis: improving admission triage. Dig Dis Sci 54: 2282-2287, 2009.
72. 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 44: 1142-1147, 1999.
73. Gironella M, Iovanna JL, Sans M, et al. Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease. Gut 54: 1244-1253, 2005.
74. Zenilman ME, Tuchman D, Zheng Q, Levine J, Delany H. Comparison of reg I and reg III levels during acute pancreatitis in the rat. Ann Surg 232: 646-652, 2000.
75. Bluth MH, Patel SA, Dieckgraefe BK, Okamoto H, Zenilman ME. Pancreatic regenerating protein (reg I) and reg I receptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis. World J Gastroenterol 12: 4511-4516, 2006.
76. Hayakawa T, Kondo T, Schibata T, et al. Serum pancreatic stone protein in pancreatic diseases. Int J Pancreatol 13: 97-103, 1993.
77. Tatemichi N, Takahashi C, Hayakawa S, et al. Enzyme immunoas-say and characterization of pancreatic stone proteins in human urine. J Clin Lab Anal 7: 365-370, 1993.
78. Verdier JM, Dussol B, Casanova P, et al. Evidence that human kidney produces a protein similar to lithostathine, the pancreatic inhibitor of CaCO3 crystal growth. Eur J Clin Invest 22: 469-474, 1992.
79. Sobajima H, Niwa T, Shikano M, et al. Urinary excretion of pancreatic stone protein in diabetic nephropathy. Intern Med 37: 500-503, 1998.
80. Nakae Y, Naruse S, Kitagawa M, et al. Molecular forms of serum pancreatic stone protein in acute pancreatitis. Int J Pancreatol 25: 17-21, 1999.
81. Satomura Y, Sawabu N, Mouri I, et al. Measurement of serum PSP/reg-protein concentration in various diseases with a newly developed enzyme-linked immunosorbent assay. J Gastroenterol 30: 643-650, 1995.
82. Keel M, Härter L, Reding T, et al. Pancreatic stone protein is highly increased during posttraumatic sepsis and activates neutro-phil granulocytes. Crit Care Med 37: 1642-1648, 2009.
83. Algül H, Treiber M, Lesina M, et al. Pancreas-specific RelA/p65 truncation increases susceptibility of acini to inflammation-associated cell death following cerulein pancreatitis. J Clin Ivest 117: 1490-1501, 2007.
84. Li L, Bimmler D, Graf R, et al. PSP/reg inhibits cultured pancreatic stellate cell and regulates MMP/TIMP ratio. Eur J Clin Invest 41: 151-158, 2011.
85. Watanabe T, Yonemura Y, Yonekura H, et al. Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein. Proc Natl Acad Sci USA 91: 3589-3592, 1994.
86. Okamoto H. The Reg gene family and Reg proteins: with special attention to the regeneration of pancreatic beta-cells. J Hepatobili-ary Pancreat Surg 6: 254-262, 1999.
87. Yamaoka T, Yoshino K, Yamada T, et al. Diabetes and tumor formation in transgenic mice expressing Reg I. Biochem Biophys Res Commun 278: 368-376, 2000.
88. Bank S, Marks IN, Vinik AI. Clinical and hormonal aspects of pancreatic diabetes. Am J Gastroenterol 64: 13-22, 1975.
89. Larsen S. Diabetes mellitus secondary to chronic pancreatits. Dan Med Bull 40: 153-162, 1993.
90. Sarles H. Chronic pancreatitis and diabetes. Baillieres Clin Endo-crinol Metab 6: 745-775, 1992.
91. Rossi L, Parvin S, Hassan Z, et al. Diabetes mellitus in tropical chronic pancreatitis is not just a secondary type of diabetes. Pan-creatology 4: 461-467, 2004.
92. Okumura N, Sakakibara A, Hayakawa T, Noda A. Pancreatic endocrine function in experimental pancreatolithiasis in dogs. Am J Gastroenterol 77: 392-396, 1982.
93. Bluth M, Mueller CM, Pierre J, et al. Pancreatic regenerating protein I in chronic pancreatitis and aging: implications for new therapeutic approaches to diabetes. Pancreas 37: 386-395, 2008.
94. Mohan V, Chari ST, Hitman GA, et al. Familial aggregation in tropical fibrocalculous pancreatic diabetes. Pancreas 4: 690-693, 1989.
95. Bhatia E, Choudhuri G, Sikora SS, et al. Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations. Gastroenterology 123: 1020-1025, 2002.
96. Mahurkar S, Reddy DN, Rao GV, Chandak GR. Genetic mechanisms underlying the pathogenesis of tropical calcific pancreatitis. World J Gastroenterol 15: 264-269, 2009.
97. Hawrami K, Mohan V, Bone A, Hitman GA. Analysis of islet regenerating (reg) gene polymorphisms in fibrocalculous pancreatic diabetes. Pancreas 14: 122-125, 1997.
98. Mahurkar S, Bhaskar S, Reddy DN, Rao GV, Chandak GR. Comprehensive screening for reg 1 alpha gene rules out association with tropical calcific pancreatitis. World J Gastroenterol 13: 5938-5943, 2007.
99. Shervani NJ, Takasawa S, Uchigata Y, et al. Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients. Eur J Clin Invest 34: 752-758, 2004.
100. Astorri E, Guglielmi C, Bombardieri M, et al. Circulating Reg 1α proteins and autoantibodies to Reg 1α proteins as biomarkers of β-cell regeneration and damage in type 1 diabetes. Horm Metab Res 42: 955-960, 2010.
101. Liu JL, Cui W, Li B, Lu Y. Possible roles of reg family proteins in pancreatic islet cell growth. Endocr Metab Immune Disord Drug Targets 8: 1-10, 2008.
102. Hou WR, Xie SN, Wang HJ, et al. Intramuscular delivery of a naked DNA plasmid encoding proinsulin and pancreatic regenerating III protein ameliorates type 1 diabetes mellitus. Pharmacol Res 63: 320-327, 2011.
103. Kimura N, Yonekura H, Okamoto H, Nagura H. Expression of human regenerating gene mRNA and its product in normal and neoplastic human pancreas. Cancer 70: 1857-1863, 1992.
104. Zenilman ME, Magnuson TH, Swinson K, Egan J, Perfetti R, Shuldiner AR. Pancreatic thread protein is mitogenic to pancreatic-derived cells in culture. Gastroenterology 110: 1208-1214, 1996.
105. Levine JL, Patel KJ, Zheng Q, Shuldiner AR, Zenilman ME. A recombinant rat regenerating protein is mitogenic to pancreatic derived cells. J Surg Res 89: 60-65, 2000.
106. Tezel E, Nagasaka T, Tezel G, et al. REG I as a marker for human pancreatic acinoductular cells. Hepatogastroenterology 51: 91-96, 2004.
107. 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 62: 1868-1875, 2002.
108. Takayama R, Nakagawa H, Sawaki A, et al. Serum tumor antigen REG4 as a diagnostic biomarker in pancreatic ductal adenocarci-noma. J Gastroenterol 45: 52-59, 2010.
109. Hayashi K, Motoyama S, Sugiyama T, et al. REG I alpha is a reliable marker of chemoradiosensitivity in squamous cell esopha-geal cancer patients. Ann Surg Oncol 15: 1224-1231, 2008.
110. Fukui H, Kinoshita Y, Maekawa T, et al. Regenerating gene protein may mediate gastric mucosal proliferation induced by hyper-gastrinemia in rats. Gastroenterology 115: 1483-1493, 1998.
111. Kinoshita Y, Ishihara S. Mechanism of gastric mucosal proliferation induced by gastrin. J Gastroenterol Hepatol 15 (Suppl): D7-D11, 2000.
112. Higham AD, Bishop LA, Dimaline R, et al. Mutations of Reg I alpha are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia. Gastroenterology 116: 1310-1318, 1999.
113. 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 128: 642-653, 2005.
114. 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 22: 906-913, 2009.
115. Zheng HC, Xu XY, Yu M, Takahashi H, Masuda S, Takano Y. The role of Reg IV gene and its encoding product in gastric car-cinogenesis. Hum Pathol 41: 59-69, 2010.
116. Kuniyasu H, Oue N, Sasahira T, et al. Reg IV enhances peritoneal metastasis in gastric carcinomas. Cell Prolif 42: 110-121, 2009.
117. Bernard-Perrone FR, Renaud WP, Guy-Crotte OM, et al. Expression of REG protein during cell growth and differentiation of two human colon carcinoma cell lines. J Histochem Cytochem 47: 863-870, 1999.
118. Zenilman ME, Kim S, Levine BA, Lee C, Steinberg JJ. Ectopic expression of reg protein: A marker of colorectal mucosa at risk for neoplasia. J Gastrointest Surg 1: 194-201, 1997.
119. Tanaka H, Fukui H, Fujii S, et al. Immunohistochemical analysis of REG Iα expression in ulcerative colitis-associated neoplastic lesions. Digestion 83: 204-209, 2011.
120. Macadam RC, Sarela AI, Farmery SM, Robinson PA, Markham AF, Guillou PJ. Death from early colorectal cancer is predicted by the presence of transcripts of the REG gene family. Br J Cancer 83: 188-195, 2000.
121. Astrosini C, Roeefzaad C, Dai YY, Dieckgraefe BK, Jöns T, Kemmner W. REG1A expression is a prognostic marker in col-orectal cancer and associated with peritoneal carcinomatosis. Int J Cancer 123: 409-413, 2008.
122. Zheng HC, Sugawara A, Okamoto H, et al. Expression profile of the REG gene family in colorectal carcinoma. J Histochem Cyto-chem 59: 106-115, 2011.
123. Hartupee JC, Zhang H, Bonaldo MF, Soares MB, Dieckgraefe BK. Isolation and characterization of a cDNA encoding a novel member of the human regenerating protein family: Reg IV. Bio-chim Biophys Acta 1518: 287-293, 2001.
124. Okamoto H, Takasawa S. Recent advances in the Okamoto model: the CD38-cyclic ADP-ribose signal system and the regenerating gene protein (Reg)-Reg receptor system in beta-cells. Diabetes 51: S462-S473, 2002.
125. Li FY, Ren XB, Xu EP, 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 11: 258-266, 2010.
126. Zhang Y, Lai M, Gu X, Luo M, Shao L. Reg IV, a differentially expressed gene in colorectal adenoma. Chin Med J 116: 918-922, 2003.
127. Bishnupuri KS, Luo Q, Korzenik JR, et al. Dysregulation of Reg gene expression occurs early in gastrointestinal tumorigenesis and regulates anti-apoptotic genes. Cancer Biol Ther 5: 1714-1720, 2006.
128. Li XH, Zheng Y, Zheng HC, et al. REG IV overexpression in an early stage of colorectal carcinogenesis: an immunohistochemical study. Histol Histopathol 25: 473-484, 2010.
129. Harada K, Zen Y, Kanemori Y, et al. Human REG I gene is up-regulated in intrahepatic cholangiocarcinoma and its precursor lesions. Hepatology 33: 1036-1042, 2001.
130. Yuan RH, Jeng YM, Chen HL, et al. Opposite roles of human pancreatitis-associated protein and REG1A expression in hepato-cellular carcinoma: association of pancreatitis-associated protein expression with low-stage hepatocellular carcinoma, beta-catenin mutation, and favorable prognosis. Clin Cancer Res 11: 2568-2575, 2005.
131. Tamura H, Ohtsuka M, Washiro M, et al. Reg IV expression and clinicopathologic features of gallbladder carcinoma. Hum Pathol 40: 1686-1692, 2009.
132. Yamauchi A, Takahashi I, Takasawa S, et al. Thiazolidinediones inhibit REG I alpha gene transcription in gastrointestinal cancer cells. Biochim Biophy Res Commun 379: 743-748, 2009.
133. Bishnupuri KS, Luo Q, Sainathan SK, et al. Reg IV regulates normal intestinal and colorectal cancer cell susceptibility to radiation-induced apoptosis. Gastroenterology 138: 616-626, 2010.
134. Zhou L, Zhang R, Wang L, et al. Upregulation of REG I alpha accelerates tumor progression in pancreatic cancer with diabetes. Int J Cancer 127: 1795-1803, 2010.
135. Takayama R, Nakagawa H, Sawaki A, et al. Serum tumor antigen REG4 as a diagnostic biomarker in pancreatic ductal adenocarci-noma. J Gastroenterol 45: 52-59, 2010.
136. Eguchi H, Ishikawa O, Ohigashi H, et al. Serum REG4 level is a predictive biomarker for the response to preoperative chemoradio-therapy in patients with pancreatic cancer. Pancreas 38: 791-798, 2009.