Pancreatic endocrine tumors: Expression profiling evidences a role for AKT-mTOR pathway

Journal of Clinical Oncology

Volumn 28, Issue 2, 2010, Pages 245-255

  Missiaglia, Edoardo ^a   Dalai, Irene ^a   Barbi, Stefano ^a   Beghelli, Stefania ^a   Falconi, Massimo ^a   Della Peruta, Marco ^a   Piemonti, Lorenzo ^a   Capurso, Gabriele ^a   Di Florio, Alessia ^a   Delle Fave, Gianfranco ^a   Pederzoli, Paolo ^a   Croce, Carlo M ^a   Scarpa, Aldo ^a  

^a UNIVERSITY OF VERONA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EVEROLIMUS; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR 13; MAMMALIAN TARGET OF RAPAMYCIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; RAPAMYCIN; SOMATOSTATIN RECEPTOR 2; TUBERIN; UNCLASSIFIED DRUG; PTEN PROTEIN, HUMAN; TUMOR SUPPRESSOR PROTEIN;

ADOLESCENT; ADULT; AGED; ARTICLE; CANCER EPIDEMIOLOGY; CANCER SURVIVAL; CELL PROLIFERATION; CONTROLLED STUDY; DOWN REGULATION; FEMALE; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; INSULINOMA; LIVER METASTASIS; MAJOR CLINICAL STUDY; MALE; PANCREAS ISLET CELL TUMOR; PRIMARY TUMOR; PRIORITY JOURNAL; PROTEIN EXPRESSION; TISSUE MICROARRAY; GENE EXPRESSION PROFILING; GENETICS; METASTASIS; MIDDLE AGED; PANCREAS ISLET CELL CARCINOMA; PANCREAS TUMOR; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ADOLESCENT; ADULT; AGED; CARCINOMA, ISLET CELL; CELL LINE, TUMOR; DOWN-REGULATION; FEMALE; GENE EXPRESSION PROFILING; HUMANS; MALE; MIDDLE AGED; NEOPLASM METASTASIS; PANCREATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS;

EID: 74949122343     PISSN: 0732183X     EISSN: None     Source Type: Journal    
DOI: 10.1200/JCO.2008.21.5988     Document Type: Article

References (59)

1. Yao JC, Eisner MP, Leary C, et al: Populationbased study of islet cell carcinoma. Ann Surg Oncol 14:3492-3500, 2007
2. Kloppel G, Perren A, Heitz PU: The gastroenteropancreatic neuroendocrine cell system and its tumors: The WHO classification. Ann N Y Acad Sci 1014:13-27, 2004
3. Bettini R, Boninsegna L, Mantovani W, et al: Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours. Ann Oncol 19:903-908, 2008
4. Pape UF, Jann H, Muller-Nordhorn J, et al: Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 113:256-265, 2008
5. Fazio N, de Braud F, Delle Fave G, et al: Interferon-alpha and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: Single agent or combination? Ann Oncol 18:13-19, 2007
6. Kwekkeboom DJ, de Herder WW, Kam BL, et al: Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: Toxicity, efficacy, and survival. J Clin Oncol 26:2124-2130, 2008
7. Panzuto F, Di Fonzo M, Iannicelli E, et al: Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma. Ann Oncol 17:461-466, 2006
8. Toumpanakis C, Meyer T, Caplin ME: Cytotoxic treatment including embolization/chemoembolization for neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab 21:131-144, 2007
9. Perren A, Wiesli P, Schmid S, et al: Pancreatic endocrine tumors are a rare manifestation of the neurofibromatosis type 1 phenotype: Molecular analysis of a malignant insulinoma in a NF-1 patient. Am J Surg Pathol 30:1047-1051, 2006
10. Eledrisi MS, Stuart CA, Alshanti M: Insulinoma in a patient with tuberous sclerosis: Is there an association? Endocr Pract 8:109-112, 2002
11. Francalanci P, Diomedi-Camassei F, Purificato C, et al: Malignant pancreatic endocrine tumor in a child with tuberous sclerosis. Am J Surg Pathol 27:1386-1389, 2003
12. Verhoef S, van Diemen-Steenvoorde R, Akkersdijk WL, et al: Malignant pancreatic tumour within the spectrum of tuberous sclerosis complex in childhood. Eur J Pediatr 158:284-287, 1999
13. Beghelli S, Pelosi G, Zamboni G, et al: Pancreatic endocrine tumours: Evidence for a tumour suppressor pathogenesis and for a tumour suppressor gene on chromosome 17p. J Pathol 186:41-50, 1998
14. Muscarella P, Melvin WS, Fisher WE, et al: Genetic alterations in gastrinomas and nonfunctioning pancreatic neuroendocrine tumors: An analysis of p16/MTS1 tumor suppressor gene inactivation. Cancer Res 58:237-240, 1998
15. Bartsch D, Hahn SA, Danichevski KD, et al: Mutations of the DPC4/Smad4 gene in neuroendocrine pancreatic tumors. Oncogene 18:2367-2371, 1999
16. Hessman O, Lindberg D, Einarsson A, et al: Genetic alterations on 3p, 11q13, and 18q in nonfamilial and MEN 1-associated pancreatic endocrine tumors. Genes Chromosomes Cancer 26:258-264, 1999
17. Moore PS, Missiaglia E, Antonello D, et al: Role of disease-causing genes in sporadic pancreatic endocrine tumors: MEN1 and VHL. Genes Chromosomes Cancer 32:177-181, 2001
18. Scarpa A, Orlandini S, Moore PS, et al: Dpc4 is expressed in virtually all primary and metastatic pancreatic endocrine carcinomas. Virchows Arch 440:155-159, 2002
19. Maitra A, Hansel DE, Argani P, et al: Global expression analysis of well-differentiated pancreatic endocrine neoplasms using oligonucleotide microarrays. Clin Cancer Res 9:5988-5995, 2003
20. Hansel DE, Rahman A, House M, et al: Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. Clin Cancer Res 10:6152-6158, 2004
21. Capurso G, Lattimore S, Crnogorac-Jurcevic T, et al: Gene expression profiles of progressive pancreatic endocrine tumours and their liver metastases reveal potential novel markers and therapeutic targets. Endocr Relat Cancer 13:541-558, 2006
22. Couvelard A, Hu J, Steers G, et al: Identification of potential therapeutic targets by geneexpression profiling in pancreatic endocrine tumors. Gastroenterology 131:1597-1610, 2006
23. Bloomston M, Durkin A, Yang I, et al: Identification of molecular markers specific for pancreatic neuroendocrine tumors by genetic profiling of core biopsies. Ann Surg Oncol 11:413-419, 2004
24. Dilley WG, Kalyanaraman S, Verma S, et al: Global gene expression in neuroendocrine tumors from patients with the MEN1 syndrome. Mol Cancer 4:9, 2005
25. Duerr EM, Mizukami Y, Ng A, et al: Defining molecular classifications and targets in gastroenteropancreatic neuroendocrine tumors through DNA microarray analysis. Endocr Relat Cancer 15:243-256, 2008
26. Piemonti L, Leone BE, Nano R, et al: Human pancreatic islets produce and secrete MCP-1/CCL2: Relevance in human islet transplantation. Diabetes 51:55-65, 2002
27. Team RDC: R: A Language and Environment for Statistical Computing. Vienna, Austria, 2005
28. Butturini G, Bettini R, Missiaglia E, et al: Predictive factors of efficacy of the somatostatin analogue octreotide as first line therapy for advanced pancreatic endocrine carcinoma. Endocr Relat Cancer 13:1213-1221, 2006
29. Hay N: The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8:179-183, 2005
30. Young J, Povey S: The genetic basis of tuberous sclerosis. Mol Med Today 4:313-319, 1998
31. Chung DC, Brown SB, Graeme-Cook F, et al: Localization of putative tumor suppressor loci by genome-wide allelotyping in human pancreatic endocrine tumors. Cancer Res 58:3706-3711, 1998
32. Rigaud G, Missiaglia E, Moore PS, et al: High resolution allelotype of nonfunctional pancreatic endocrine tumors: Identification of two molecular subgroups with clinical implications. Cancer Res 61: 285-292, 2001
33. Eng C: PTEN: One gene, many syndromes. Hum Mutat 22:183-198, 2003
34. Perren A, Komminoth P, Saremaslani P, et al: Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. Am J Pathol 157:1097-1103, 2000
35. Kaper F, Dornhoefer N, Giaccia AJ: Mutations in the PI3K/PTEN/TSC2 pathway contribute to mammalian target of rapamycin activity and increased translation under hypoxic conditions. Cancer Res 66:1561-1569, 2006
36. Couvelard A, O'Toole D, Turley H, et al: Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: Negative correlation of microvascular density and VEGF expression with tumour progression. Br J Cancer 92:94-101, 2005
37. Marion-Audibert AM, Barel C, Gouysse G, et al: Low microvessel density is an unfavorable histoprognostic factor in pancreatic endocrine tumors. Gastroenterology 125:1094-1104, 2003
38. Tuttle RL, Gill NS, Pugh W, et al: Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha. Nat Med 7:1133-1137, 2001
39. Rachdi L, Balcazar N, Osorio-Duque F, et al: Disruption of Tsc2 in pancreatic beta cells induces beta cell mass expansion and improved glucose tolerance in a TORC1-dependent manner. Proc Natl Acad Sci U S A 105:9250-9255, 2008
40. Guo SS, Wu X, Shimoide AT, et al: Frequent overexpression of cyclin D1 in sporadic pancreatic endocrine tumours. J Endocrinol 179:73-79, 2003
41. Radu A, Neubauer V, Akagi T, et al: PTEN induces cell cycle arrest by decreasing the level and nuclear localization of cyclin D1. Mol Cell Biol 23: 6139-6149, 2003
42. Zacharek SJ, Xiong Y, Shumway SD: Negative regulation of TSC1-TSC2 by mammalian D-type cyclins. Cancer Res 65:11354-11360, 2005
43. Zhang H, Cicchetti G, Onda H, et al: Loss of Tsc1/Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR. J Clin Invest 112:1223-1233, 2003
44. Zhang H, Bajraszewski N, Wu E, et al: PDGFRs are critical for PI3K/Akt activation and negatively regulated by mTOR. J Clin Invest 117:730-738, 2007
45. Harrington LS, Findlay GM, Gray A, et al: The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol 166:213-223, 2004
46. Shah OJ, Wang Z, Hunter T: Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr Biol 14:1650-1656, 2004
47. Ma L, Teruya-Feldstein J, Behrendt N, et al: Genetic analysis of Pten and Tsc2 functional interactions in the mouse reveals asymmetrical haploinsufficiency in tumor suppression. Genes Dev 19: 1779-1786, 2005
48. Neshat MS, Mellinghoff IK, Tran C, et al: Enhanced sensitivity of PTEN-deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci U S A 98:10314-10319, 2001
49. Podsypanina K, Lee RT, Politis C, et al: An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc Natl Acad Sci U S A 98:10320-10325, 2001
50. Grozinsky-Glasberg S, Franchi G, Teng M, et al: Octreotide and the mTOR inhibitor RAD001 (everolimus) block proliferation and interact with the Akt-mTOR-p70S6K pathway in a neuro-endocrine tumour cell line. Neuroendocrinology 87:168-181, 2008
51. Zitzmann K, De Toni EN, Brand S, et al: The novel mTOR inhibitor RAD001 (everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells. Neuroendocrinology 85:54-60, 2007
52. O'Reilly KE, Rojo F, She QB, et al: MTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res 66:1500-1508, 2006
53. Maira SM, Stauffer F, Brueggen J, et al: Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther 7:1851-1863, 2008
54. Duran I, Kortmansky J, Singh D, et al: A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Br J Cancer 95:1148-1154, 2006
55. O'Donnell PH, Ratain MJ: Evaluating the activity of temsirolimus in neuroendocrine cancer. Br J Cancer 96:177, 2007; author reply 178-179, 2007
56. Yao JC, Phan AT, Chang DZ, et al: Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: Results of a phase II study. J Clin Oncol 26:4311-4318, 2008
57. Olsen SK, Garbi M, Zampieri N, et al: Fibroblast growth factor (FGF) homologous factors share structural but not functional homology with FGFs. J Biol Chem 278:34226-34236, 2003
58. Schoorlemmer J, Goldfarb M: Fibroblast growth factor homologous factors and the islet brain-2 scaffold protein regulate activation of a stress-activated protein kinase. J Biol Chem 277: 49111-49119, 2002
59. Bernards R, Weinberg RA: A progression puzzle. Nature 418:823, 2002