The molecular basis of pancreatic cancer

Annals of Gastroenterology

Volumn 13, Issue 3, 2000, Pages 188-195

  Koliopanos, A ^a   Friess, Helmut ^a   Ozawa, F ^a   Kleeff, J ^a   Buchler M ^a  

^a UNIVERSITY OF BERN   (Switzerland)

Author keywords

Genes; Growth factors; Molecular alterations; Pancreatic cancer; Transcription factors

Indexed keywords

CD82 ANTIGEN; EPIDERMAL GROWTH FACTOR; EPIDERMAL GROWTH FACTOR RECEPTOR; FAS LIGAND; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR RECEPTOR; FRAGILE HISTIDINE TRIAD PROTEIN; INHIBITOR OF DIFFERENTIATION 2; K RAS PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE 1; NERVE GROWTH FACTOR; NERVE GROWTH FACTOR RECEPTOR; PLATELET DERIVED GROWTH FACTOR; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN BAX; PROTEIN BCL 2; PROTEIN P16; PROTEIN P53; RAF PROTEIN; RAS PROTEIN; SMAD4 PROTEIN; SOMATOMEDIN; SOMATOMEDIN RECEPTOR; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TUMOR NECROSIS FACTOR ALPHA;

AMINO ACID SUBSTITUTION; ARTICLE; CANCER INVASION; CARCINOGENESIS; CELL PROLIFERATION; CHEMOTHERAPY; GENE EXPRESSION; GENE MUTATION; GENE OVEREXPRESSION; GENETIC TRANSCRIPTION; HORMONAL THERAPY; HUMAN; IMMUNOTHERAPY; METASTASIS; PANCREAS CARCINOMA; POINT MUTATION; PROGNOSIS; PROTEIN DETERMINATION; PROTEIN FUNCTION; SURVIVAL RATE; TRANSCRIPTION REGULATION; TUMOR GROWTH;

EID: 34548329304     PISSN: 11087471     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (126)

1. Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1997. CA Cancer J Clin 1997; 47:5-27.
2. Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs. fluorouracil and doxorubicin vs. fluorouracil, doxorubicin, and mitomycin. JAMA 1985; 253:2061-2067.
3. Moertel CG, Frytak S, Hahn RG, O'Connell MJ, Reitemeier Rubin RJ, Schutt AJ, Weiland LH, Childs DS, Holbrook MA, Lavin PT, Livstone E, Spiro H, Knowlton A, Kalser M, Barkin J, Lessner H, Mann-Kaplan R, Ramming K, Douglas HO Jr, Thomas P, Nave H, Bateman J, Lokich J, Brooks J, Chaffey J, Corson JM, Zamcheck N, Novak JW. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 1981; 48:1705-1710.
4. Poen JC, Ford JM, Niederhuber JE. Chemoradiotherapy in the management of localized tumors of the pancreas. Ann Surg Oncol 1999; 6:117-122.
5. White R, Lee C, Anscher M, Gottfried M, Wolff R, Keogan M, Pappas T, Hurwitz H, Tyler D. Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Ann Surg Oncol 1999; 6:38-45.
6. Takahashi S, Aiura K, Saitoh J, Hayatsu S, Kitajima M, Ogata Y. Treatment strategy for pancreatic head cancer: pylorus-preserving pancreatoduodenectomy, intraoperative radiotherapy and portal catheterization. Digestion 1999; 60:130-134.
7. Friess H, Büchler M, Kruger M, Beger HG. Related Articles Treatment of duct carcinoma of the pancreas with the LH-RH analogue buserelin. Pancreas 1992; 7:516-521.
8. Friess H, Büchler M, Beglinger C, Weber A, Kunz J, Fritsch K, Dennler HJ, Beger HG. Low-dose octreotide treatment is not effective in patients with advanced pancreatic cancer. Pancreas 1993; 8:540-545.
9. Büchler M, Friess H, Schultheiss KH, Gebhardt C, Kubel R, Muhrer KH, Winkelmann M, Wagener T, Klapdor R, Kaul M. A randomized controlled trial of adjuvant immunotherapy (murine monoclonal antibody 494/32) in resectable pancreatic cancer. Cancer 1991; 68:1507-1512.
10. Longnecker DS, Terhune PG. What is the true rate of K-ras mutation in carcinoma of the pancreas? Pancreas 1998; 17:323-324.
11. Lemoine NR, Jain S, Hughes CM, Staddon SL, Maillet B, Hall PA, Kloppel G. Ki-ras oncogene activation in pre-invasive pancreatic cancer. Gastroenterology 1992; 102:230-236.
12. Casey G, Yamanaka Y, Friess H, Kobrin MS, Lopez ME, Büchler M, Beger HG, Korc M. p53 mutations are common in pancreatic cancer and are absent in chronic pancreatitis. Cancer Lett 1993; 69:151-160.
13. Scarpa A, Capelli P, Mukai K, Zamboni G, Oda T, Iacono C, Hirohashi S. Pancreatic adenocarcinomas frequently show p53 gene mutations. Am J Pathol 1993; 142:1534-1543.
14. Barton CM, Staddon SL, Hughes CM, Hall PA, O'Sullivan C, Kloppel G, Theis B, Russell RC, Neoptolemos J, Williamson RC. Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer. Br J Cancer 1991; 64:1076-1082.
15. Kasuya K, Watanabe H, Nakasako T, Ajioka. Y, Koyanagi Y. p53 protein overexpression and K-ras codon 12 mutation in pancreatic ductal carcinoma: correlation with histologic factors. Pathol Int 1997; 47:531-539.
16. Harada N, Gansauge S, Gansauge F, Gause H, Shimoyama S, Imaizumi T, Mattfeld T, Schoenberg MH, Beger HG. Nuclear accumulation of p53 correlates significantly with clinical features and inversely with the expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in pancreatic cancer. Br J Cancer 1997; 76:299-305.
17. Nakamori S, Yashima K, Murakami Y, Ishikawa O, Ohigashi H, Imaoka S, Yaegashi S, Konishi Y, Sekiya T. Association of p53 gene mutations with short survival in pancreatic adenocarcinoma. Jpn J Cancer Res 1995; 86:174-181.
18. Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Gruban RH, Kern SE. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 1996; 271:350-353.
19. Grau AM, Zhang L, Wang W, Ruan S, Evans DB, Abbruzzese JL, Zhang W, Chiao PJ. Induction of p21waf1 expression and growth inhibition by transforming growth factor beta involve the tumor suppressor gene DPC4 in human pancreatic adenocarcinoma cells. Cancer Res 1997; 57:3929-3934.
20. Caldas C, Hahn SA, Dacosta LT, Redston MS, Schutte M, Seymour AB, Weinstein CL, Hruban RH, Yeo CJ, Kern SE. Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma. Nat Genet 1994; 8:27-32.
21. Friess, H, Lu Z, Graber HU, Zimmermann A, Adler G, Korc M, Schmid RM, Büchler MW. bax, but not bcl-2, influences the prognosis of human pancreatic cancer. Gut. 1998; 43:414-421.
22. L worsens the prognosis in pancreatic cancer. Ann Surg 1998; 228:780-787.
23. Raitano AB, Scuderi P, Korc M. Binding and biological effects of tumor necrosis factor and gamma interferon in human pancreatic carcinoma cells. Pancreas 1990; 5:267-277.
24. Ungefroren H, Voss M, Jansen M, Roeder C, Henne-Bruns D, Kremer B, Kalthoff H. Human pancreatic adenocarcinomas express Fas and Fas ligand yet are resistant to Fas-mediated apoptosis. Cancer Res 1998; 58:1741-1749.
25. Kleeff J, Ishiwata T, Friess H, Büchler MW, Israel MA, Korc M. The helix-loop-helix protein Id2 is overexpressed. in human pancreatic cancer. Cancer Res 1998; 58:3769-3772.
26. Guo X, Friess H, Graber HU, Kashiwagi M, Zimmermann A, Korc M, Buchler MW. KAI1 expression is u-regulated in early pancreatic cancer and decreased in the presence of metastases. Cancer Res 1996; 56:4876-4880.
27. Friess H, Guo XZ, Berberat P, Graber HU, Zimmermann A, Korc M, Büchler MW. Reduced KAI1 expression in pancreatic cancer is associated with lymph node and distant metastases. Int J Cancer 1998; 79:349-355.
28. Simon B, Bartsch D, Barth P, Prasnikar N, Munch K, Blum A, Arnold R, Goke B. Frequent abnormalities of the putative tumor suppressor gene FHIT at 3p14.2 in pancreatic carcinoma cell lines. Cancer Res 1998; 58:1583-1587.
29. Hruban RH, Wilentz RE, Goggins M, Offerhaus GJ, Yeo CJ, Kern SE. Pathology of incipient pancreatic cancer. Ann Oncol 1999; 10 Suppl 4:9-11.
30. Hruban RH, Petersen GM, Goggins M, Tersmette AC, Offerhaus GJ, Falatko F, Yeo CJ, Kern SE. Familial pancreatic cancer. Ann Oncol 1999; 10 Suppl 4:69-73.
31. White R, Lee C, Anscher M, Gottfired M, Wolff R, Keogan M, Pappas T, Hurwitz H, Tyler D. Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Ann Surg Oncol 1999;6:38-45.
32. Takahashi S, Aiura K, Saitoh J, Hayatsu S, Kitajima M, Ogata Y. Treatment strategy for pancreatic head cancer: Pylorus-preserving pancreatoduodenectomy, intraoperative radiotherapy and portal catheterization. Digestion 1999; 60:130-134.
33. Massague J. TGF-beta signal transduction. Annu Rev Biochem 1998; 67:753-791.
34. Derynck R, Feng XH. TGF-beta receptor signaling. Biochim Biophys Acta 1997; 1333:105-150.
35. Heldin CH, Miyazono Y, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997; 390:465-471.
36. Wang XF, Lin HY, Ng-Eaton E, Downward J, Lodish HF, Weinberg RA. Expression cloning and characterization of the TGF-beta type III receptor. Cell 1991; 67:797-805.
37. Lopez-Casillas F, Cheifetz S, Doody J, Andres JL, Lane WS, Massague J. Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system. Cell 1991; 67:785-795.
38. Heldin CH, Miyazono K, ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997; 390:465-471.
39. Derynck R, Zhang Y, Feng XH. Smads: transcriptional acivators of TGF-beta responses. Cell 1998; 95:737-740.
40. Kretzschmar M, Massague J. SMADs: mediators and regulators of TGF-beta signaling. Curr Opin Genet Dev 1998; 8:103-111.
41. Whitman M. Signal transduction. Feedback from inhibitory SMADs. Nature 1997; 389:549-551.
42. Kretzschmar M, Liu F, Hata A, Doody J, Massague J. The TGF-beta family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase. Genes Dev 1997; 11:984-995.
43. Macias-Silva M, Hoodless PA, Tang SJ, Buchwald M, Wrana JL. Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2. J Biol Chem 1998; 273:25628-25636.
44. Yamamoto N, Akiyama S, Katagiri T, Namiki M, Kurokawa T, Suda T. Smad1 and smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts. Biochem Biophys Res Commun 1997; 238:574-580.
45. Friess H, Yamanaka Y, Büchler M, Ebert M, Beger HG, Gold LI, Korc M. Enhanced expression of transforming growth factor beta isoforms in pancreatic cancer correlates with decreased survival. Gastroenterology 1993; 105:1846-1856.
46. Friess H, Yamanaka Y, Büchler M, Berger HG, Kobrin MS, Baldwin RL, Korc M. Enhanced expression of the type II transforming growth factor beta receptor in human pancreatitis cancer cells without alteration of type III receptor expression. Cancer Res 1993; 53:2704-2707.
47. Lu Z, Friess H, Graber HU, Guo X, Schilling M, Zimmermann A, Korc M, Büchler MW. Presence of two signaling TGF-beta receptors in human pancreatic cancer correlates with advanced tumor stage. Dig Dis Sci 1997; 42:2054-2063.
48. Baldwin RL, Friess H, Yokoyama M, Lopez ME, Kobrin MS, Büchler MW, Korc M. Attenuated ALK5 receptor expression in human pancreatic cancer: correlation with resistance to growth inhibition. Int J Cancer 1996; 67:283-288.
49. Kleeff J, Korc M. Up-regulation of transforming growth factor (TGF)-beta receptors by TGF-beta1 in COLO-357 cells. J Biol Chem 1998; 273:7495-7500.
50. Wagner M, Kleeff J, Lopez ME, Bockman I, Massague J, Korc M. Transfetion of the type I TGF-beta receptor restores TGF-beta responsiveness in pancreatic cancer. Int J Cancer 1998; 78:255-260.
51. Kleeff J, Maruyama H, Friess H, Büchler MW, Falb D, Korc M. Smad6 suppresses TGF-beta-induced growth inhibition in COLO-357 pancreatic cancer cells and is overexpressed in pancreatic cancer. Biochem Biophys Res Commun 1999; 255:268-273.
52. Kleeff J, Ishiwata T, Maruyama H, Friess H, Truong P, Büchler MW, Falb D, Korc M. The TGF-beta signaling inhibitor Smad7 enhances tumorigenicity in pancreatic cancer. Oncogene 1999; 18:5363-5372.
53. Kleeff J, Ishiwata T, Friess H, Büchler MW, Korc M. Concomitant over-expression of activin/inhibin beta subunits and their receptors in human pancreatic cancer. Int J Cancer 1998; 77:860-868.
54. Kleeff J, Maruyama H, Ishiwata T, Sawhney H, Friess H, Büchler MW, Korc M. Bone morphogenetic protein 2 exerts diverse effects on cell growth in vitro and is expressed in human pancreatic cancer in vivo. Gastroenterology 1999; 116:1202-1216.
55. Guide book to cytokines and their receptors. Nicos a Nicola edi. New York: Oxford Univesity Press Inc., 1994.
56. Laurence DJ, Gusterson BA. The epidermal growth factor. A review of structural and functional relationships in the normal organism and in cancer cells. Tumour Biol 1990; 11:229-261.
57. Carraway KL 3rd, Weber JL, Unger MJ, Ledesma J, Yu N, Gassmann M, Lai C. Neuregulin-2, a new ligand of ErbB3/ErbB4-receptor tyrosine kinases. Nature 1997; 387:512-516.
58. Chang H, Riese DJ 2nd, Gilbert W, Stern DF, McMahan UJ. Ligands for ErbB-family receptors encoded by a neuregulin-like gene. Nature 1997; 387:509-512.
59. Davis-Fleischer KM, Besner GE. Structure and function of heparin-binding EGF-like growth factor (HB-EGF). Front Biosci 1998; 3:288-299.
60. Derynck R. The physiology of transforming growth factor-alpha. Adv Cancer Res 1992 58:27-52.
61. Kudlow JE, Bjorge JD. TGF alpha in normal physiology. Semin Cancer Biol 1990; 1:293-302.
62. Plowman GD, Green JM, McDonald VL, Neubauer MG, Disteche CM, Todaro GJ, Shoyab M. The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity. Mol Cell Biol 1990; 10:1969-1981.
63. Sasada R, One Y, Taniyama Y, Shing Y, Fokman J, Igarashi K. Cloning and expression of cDNA encoding human betacellulin, a new member of the EGF family. Biochem Biophys Res Commun 1993; 190:1173-1179.
64. Toyoda H, Komurasaki T, Uchida D, Morimoto S. Distribution of mRNA for human epiregulin, a differentially expressed member of the epidermal growth factor family. Biochem J 1997; 326:69-75.
65. Zhang D, Sliwkowski MX, Mark M, Frantz G, Akita R, Sun Y, Hillan K, Crowley C, Brush J, Godowski PJ. Neuregulin-3 (NRG3): a novel neural tissue-enriched protein that binds and activates ErbB4. Proc Nad Acad Sci USA 1997; 94:9562-9567.
66. Carpenter G, Wahl MI. Peptide growth factors and their receptors. Sporn MB, Roberts AB (eds) Berlin, Springer, 1990, pp 69-171.
67. Sarkar FH, Ball DE, Li YW, Crissman JD. Molecular cloning and sequencing of an intron of Her-2/neu (ERBB2) gene. DNA Cell Biol 1993; 12,611-615.
68. Prigent SA, Lemoine NR. The type 1 (EGFR-related) family of growth factor receptors and their ligands. Prog Growth Factor Res 1992; 4:1-24.
69. Kraus MH, Issing W, Miki T, Popescu NC, Aaronson SA. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci USA 1989; 86:9193-9197.
70. Carraway KL 3rd, Cantley LC. A new acquaintance for erbB3 and erbB4: a role for receptor heterodimerization in growth signaling. Cell 1994; 78:5-8.
71. Koch CA, Anderson D, Moran MF, Ellis C, Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science 1991; 252:668-674.
72. van der Heyden MA, Van Bergen en Henegouwen PM, de Ruiter N, Verdaasdonk MA van den Tweel JG, Rijksen G, Boonstra J, Joling P. The actin binding domain of the epidermal growth factor receptor is required for EGF-stimulated tissue invasion. Exp Cell Res 1997; 234:521-526.
73. Riese DJ 2nd, Stern DF. Specificity within the EGF family/ErbB receptor family signaling network. Bioessays, 1998; 20:41-48.
74. Yamada M, Ikeuchi T, Hatanaka H. The neurotrophic action and signalling of epidermal growth factor. Prog Neurobiol 1997; 51:19-37.
75. Cano E, Mahadevan LC. Parallel signal processing among mammalian MAPKs. Trends Biochem. Sci 1995; 20:117-122.
76. Errede B, Cade RM, Yashar BM, Kamada Y, Levin DE, Irie K, Matsumoto K. Dynamics and organization of MAP kinase signal pathways. Mol Reprod Dev 1995; 42:477-485.
77. Fanger GR, Gerwins P, Widmann C, Jarpe MB, Johnson GL. MEKKs, GCKs, MLKs, PAKs, TAKs, and tpls: upstream regulators of the c-Jun amino-terminal kinases? Curr Opin Genet Dev 1997; 7:67-74.
78. Schlesinger TK, Fanger GR, Yujiri T, Johnson GL. The TAO of MEKK, Front Biosci 1998; 3:1181-1186.
79. Seger R, Krebs EG. The MAPK signaling cascade. FASEB J 1995; 9:726-735.
80. Friess H, Yamanaka Y, Kobrin MS, Do DA, Büchler MW, Korc M. Enhanced erbB-3 expression in human pancreatic cancer correlates with tumor progression. Clin Cancer Res 1995; 1:1413-1420.
81. Barton CM, Hall PA, Hughes CM, Gullick WJ, Lemoine NR. Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer. J Pathol 1991, 163:111-116.
82. Korc M, Chandrasekar B, Yamanaka Y, Friess H, Büchler M, Beger HG. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Invest 1992; 90:1352-1360.
83. Yamanaka Y, Friess H, Kobrin MS, Büchler M, Beger HG, Korc M. Coexpression of epidermal growth factor receptor and ligands in human pancreatic cancer is associated with enhanced tumor aggressiveness. Anticancer Res 1993; 13:565-569.
84. Korc M. Role of growth factors in pancreatic cancer. Surg Oncol Clin N Am 1998; 7:25-41.
85. Lemoine NR, Hall PA. Growth factors and oncogenes in pancreatic cancer. Baillieres Clin Gastroenterol 1990; 4:815-832.
86. Wagner M, Luhrs H, Kloppel G, Adler G, Schmid Rm. Malignant transformation of duct-like cells originating from acini in transforming growth factor transgenic mice. Gastroenterology 1998; 115:1254-1262.
87. Wagner M, Cao T, Lopez ME, Hope C, van Nostrand K, Kobrin MS, Fan HU, Büchler MW, Korc M. Expression of a truncated EGF receptor is associated with inhibition of pancreatic cancer cell growth and enhanced sensitivity to cisplatinum. Int J Cancer 1996; 68:782-787.
88. Basilico C, Moscatelli D. The FGF family of growth factors and oncogenes. Adv Cancer Res 1992; 59:115-165.
89. Demo SD, Kikuchi A, Peters KG, MacNicol AM, Muslin AJ, Williams LT. Signaling molecules that mediate the actions of FGF. Princess Takamatsu Symp 1994; 24:243-249.
90. Givol D, Yayon A. Complexity of FGF receptors: genetic basis for structural diversity and functional specificity. FASEB J 1992; 6:3362-3369.
91. Johnson DE, Williams LT. Structural and functional diversity in the FGF receptor multigene family. Adv Cancer Res 1993; 60:1-41.
92. Kornmann M, Beger HG, Korc M. Role of fibrobast growth factors and their receptors in pancreatic cancer and chronic pancreatitis. Pancreas. 1998; 17:169-175.
93. Partanen J, Vainikka S, Alitalo K. Structural and functional specificity of FGF receptors. Philos Trans R Soc Lond B Biol Sci 1993; 340:297-303.
94. Kornmann M, Ishiwata T, Beger HG, Korc M. Fibroblast growth factor-5 stimulates mitogenic signaling and is over-expressed in human pancreatic cancer: evidence for autocrine and paracrine actions. Oncogene 1997; 15:1417-1424.
95. Yamanaka Y, Friess H, Büchler M, Beger HG, Uchida E, Onda M, Kobrin MS, Korc M. Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage. Cancer Res 1993; 53:5289-5296.
96. Kobrin MS, Yamanaka Y, Friess H, Lopez ME, Korc M. Aberrant expression of type I fibroblast growth factor receptor in human pancreatic adenocarcinomas. Cancer Res 1993; 53:4741-4744.
97. Ishiwata T, Friess H, Büchler MW, Lopez ME, Korc M. Characterization of keratinocyte growth factor and receptor expression in human pancreatic cancer. Am J Pathol 1998; 153:213-222.
98. Kleeff J, Ishiwata T, Kumbasar A, Friess H, Büchler MW, Lander AD, Korc M. The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer. J Clin Invest 1998; 102:1662-1673.
99. Wagner M, Lopez ME, Cahn M, Korc M. Suppression of fibroblast growth factor receptor signaling inhibits pancreatic cancer growth in vitro and in vivo. Gastroenterology 1998; 114:798-807.
100. Levi-Montalcini R. The nerve growth factor 35 years later. Science 1987; 237:1154-1162.
101. Bold RJ, Ishizuka J, Rajaraman S, Perez-Polo JR, Townsend CM Jr, Thompson JC. Nerve growth factor as a mitogen for a pancreatic carcinoid cell line. J Neurochem 1995; 64:2622-2628.
102. Oelmann E, Sreter L, Schuller I, Serve H, Koenigsmann M, Wiedenmann B, Oberberg D, Reufi B, Thiel E, Berdel WE. Nerve growth factor stimulates clonal growth of human lung cancer cell lines and a human glioblastoma cell line expressing high-affinity nerve growth factor binding sites involving tyrosine kinase signaling. Cancer Res 1995; 55:2212-2219.
103. Geldof AA, De Kleijn MA, Rao BR, Newling DW. Nerve growth factor stimulates in vitro invasive capacity of DU145 human prostatic cancer cells. J Cancer Res Clin Oncol 1997; 123:107-112.
104. Klein R, Jing SQ, Nanduri V, O'Rourke E, Barbacid M. The trk proto-oncogene encodes a receptor for nerve growth factor. Cell 1991; 65:189-197.
105. Zhu Z, Friess, H, diMola FF, Zimmermann A, Graber HU, Korc M, Büchler MW. Nerve growth factor expression correlates with perineural invasion and pain in human pancreatic cancer. J Clin Oncol 1999; 17:2419-2428.
106. Pour PM, Egami H, Takiyama Y. Patterns of growth and metastases of induced pancreatic cancer in relation to the prognosis and its clinical implications. Gastroenterology 1991; 100:529-536.
107. Gudjonsson B. Cancer of the pancreas. 50 years of surgery. Cancer 1987; 60:2284-2303.
108. Bockman DE, Büchler MW, Beger HG. Morphology of pancreatic cancer: Involvement of nerves, in Beger HG, Büchler MW, Schoenberg M (eds): Cancer of pancreas. Ulm Germany, Universitätsverlag Ulm GmbH, 1996, pp 99-108.
109. Westermark B, Heldin CH. Platelet-derived growth factor in autocrine transformation. Cancer Res 1991; 51:5087-5092.
110. Ebert M, Yokoyama M, Friess H, Kobrin MS, Büchler MW, Korc M. Induction of platelet-derived growth factor A and B chains and over-expression of their receptors in human pancreatic cancer. Int J Cancer 1995; 62:529-535.
111. Wetterau LA, Moore MG, Lee KW, Shim ML, Cohen P. Novel aspects of the insulin-like growth factor binding proteins. Mol Genet Metab 1999; 68:161-181.
112. Roberts CT Jr, Leroith D. Molecular aspects of insulin-like growth factors, their binding proteins and receptors. Baillieres Clin Endocrinol Metab 1988; 2:1069-1085.
113. el-Roeiy A, Chen X, Roberts VJ, Shimasakai S, Ling N, LeRoith D, Roberts CT Jr, Yen SS. Expression of the genes encoding the insulin-like growth factors (IGF-I and II), the IGF and insulin receptors, and IGF-binding proteins-1-6 and the localization of their gene products in normal and polycystic ovary syndrome ovaries. J Clin Endocrinol Metab 1994; 78:1488-1496.
114. Bergmann U, Funatomi H, Yokoyama M, Beger HG, Korc M. Insulin-like growth factor I overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles. Cancer Res 1995; 55:2007-2011.
115. Ohmura E, Okada M, Onoda N, Kamiya Y, Murakami H, Tsushima T, Shizume K. Insulin-like growth factor I and transforming growth factor alpha as autocrine growth factors in human pancreatic cancer cell growth. Cancer Res 1990; 50:103-107.
116. Cox PM, Goding CR. Transcription and cancer. Br J Cancer 1991; 63:651-662.
117. Liu AY, Corey E, Vessella RL, Lange PH, True LD, Huang GM, Nelson PS, Hood L. Identification of differentially expressed prostate genes: increased expression of transcription factor ETS-2 in prostate cancer. Prostate 1997; 30:145-153.
118. Benz CC, O'Hagan RC, Richter B, Scott GK, Chang CH, Xiong X, Chew K, Ljung BM, Edgerton S, Thor A, Hassell JA. HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer. Oncogene 1997; 15:1513-1525.
119. Schmid RM, Liptay S, Weidenbach H, Adler G, Transcription factors in pancreatic cancer. Dig Surg 1994; 11:160-163.
120. Murre C, McCaw PS, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell 1989; 56:777-783.
121. Davis RL, Cheng PF, Lassar AB, Weintraub H. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell 1990; 60:733-746.
122. Wakita, Y., Ohyanagi H, Yamamoto K, Tokuhisa, T, Saitoh Y. Overexpression of c-Ki-ras and c-fos in human pancreatic carcinomas. Int J Pancreatol 1992; 11:43-47.
123. Lee CS, Charalambous D. Immunohistochemical localisation of the c-fos oncoprotein in- pancreatic cancers. Zentralbl Pathol 1994;140:271-275.
124. Schafer H, Zheng J, Gundlach F, Gunther R, Schmidt WE. PACAP stimulates transcription of c-Fos and c-Jun and activates the AP-1 transcription factor in rate pancreatic carcinoma cells. Biochem Biophys Res Commun 1996; 221:111-116.
125. Fields S, Jang SK. Presence of a potent transcription activating sequence in the p53 protein. Science 1990; 249:1046-1049.
126. Raycroft L, Wu HY, Lozano G. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science 1990; 249:1049-1051.