PI3K signaling maintains c-myc expression to regulate transcription of E2F1 in pancreatic cancer cells

Molecular Carcinogenesis

Volumn 48, Issue 12, 2009, Pages 1149-1158

  Schild, Carolin ^a   Wirth, Matthias ^a   Reichert, Maximilian ^a   Schmid, Roland M ^a   Saur, Dieter ^a   Schneider, Günter ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

AKT; c myc; E2F; Pancreatic cancer; PI3K

Indexed keywords

GLYCOGEN SYNTHASE KINASE 3; MYC PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; TRANSCRIPTION FACTOR E2F1; MESSENGER RNA;

ARTICLE; CANCER CELL; CELL CYCLE PROGRESSION; CELL CYCLE S PHASE; CONTROLLED STUDY; GENE EXPRESSION REGULATION; HUMAN; HUMAN CELL; PANCREAS CANCER; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; UPREGULATION; CELL CYCLE G1 PHASE; CHROMATIN IMMUNOPRECIPITATION; GENETIC TRANSCRIPTION; GENETICS; METABOLISM; PANCREAS CARCINOMA; PANCREAS TUMOR; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; TUMOR CELL CULTURE; WESTERN BLOTTING;

1-PHOSPHATIDYLINOSITOL 3-KINASE; BLOTTING, WESTERN; CARCINOMA, PANCREATIC DUCTAL; CHROMATIN IMMUNOPRECIPITATION; E2F1 TRANSCRIPTION FACTOR; G1 PHASE; GLYCOGEN SYNTHASE KINASE 3; HUMANS; PANCREATIC NEOPLASMS; PROMOTER REGIONS, GENETIC; PROTO-ONCOGENE PROTEINS C-MYC; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; S PHASE; SIGNAL TRANSDUCTION; TRANSCRIPTION, GENETIC; TUMOR CELLS, CULTURED;

EID: 73349115238     PISSN: 08991987     EISSN: 10982744     Source Type: Journal    
DOI: 10.1002/mc.20569     Document Type: Article

References (47)

1. Schneider G, Siveke JT, Eckel F, Schmid RM. Pancreatic cancer: Basic and clinical aspects. Gastroenterology 2005;128:1606-1625.
2. Mitry E, Rachet B, Quinn MJ, Cooper N, Coleman MP. Survival from cancer of the pancreas in England and Wales up to 2001. Br J Cancer 2008;99:S21-S23.
3. Eilers M, Eisenman RN. Myc's broad reach. Genes Dev 2008; 22:2755-2766.
4. Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev 2008;8:976-990.
5. Schleger C, Verbeke C, Hildenbrand R, Zentgraf H, Bleyl U. c-MYC activation in primary and metastatic ductal adenocarcinoma of the pancreas: Incidence, mechanisms, and clinical significance. Mod Pathol 2002;15:462-469.
6. Li YJ, Wei ZM, Meng YX, Ji XR. Beta-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: Relationships with carcinogenesis and metastasis. World J Gastroenterol 2005;11:2117-2123.
7. Sandgren EP, Quaife CJ, Paulovich AG, Palmiter RD, Brinster RL. Pancreatic tumor pathogenesis reflects the causative genetic lesion. Proc Natl Acad Sci USA. 1991;88:93-97.
8. Mahlamaki EH, Barlund M, Tanner M, et al. Frequent amplification of 8q24, 11q, 17q, and 20q-specific genes in pancreatic cancer. Genes Chromosomes Cancer 2002;35:353-358.
9. Buchholz M, Schatz A, Wagner M, et al. Overexpression of c-myc in pancreatic cancer caused by ectopic activation of NFATc1 and the Ca2+/calcineurin signaling pathway. EMBO J 2006;25:3714-3724.
10. Zhao L, Vogt PK. Class I PI3K in oncogenic cellular transformation. Oncogene 2008;27:5486-5496.
11. Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS, Workman P. Targeting the PI3K-AKT-mTOR pathway: Progress, pitfalls, and promises. Curr Opin Pharmacol 2008;8:393-412.
12. Schlieman MG, Fahy BN, Ramsamooj R, Beckett L, Bold RJ. Incidence, mechanism and prognostic value of activated AKT in pancreas cancer. Br J Cancer 2003;89:2110-2115.
13. Pham NA, Schwock J, Iakovlev V, Pond G, Hedley DW, Tsao MS. Immunohistochemical analysis of changes in signaling pathway activation downstream of growth factor receptors in pancreatic duct cell carcinogenesis. BMC Cancer 2008;8:43.
14. Asano T, Yao Y, Zhu J, Li D, Abbruzzese JL, Reddy SA. The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-kappaB and c-Myc in pancreatic cancer cells. Oncogene 2004;23:8571-8580.
15. Reichert M, Saur D, Hamacher R, Schmid RM, Schneider G. Phosphoinositide-3-kinase signaling controls S-phase kinase-associated protein 2 transcription via E2F1 in pancreatic ductal adenocarcinoma cells. Cancer Res 2007;67:4149-4156.
16. Lin CY, Liang YC, Yung BY-M. Nucleophosmin/B23 regulates transcriptional activation of E2F1 via modulating the promoter binding of NF-kappaB, E2F1 and pRB. Cell Signal 2006;18:2041-2048.
17. Schneider G, Saur D, Siveke JT, Fritsch R, Greten FR, Schmid RM. IKKalpha controls p52/RelB at the skp2 gene promoter to regulate G1- to S-phase progression. EMBO J 2006;25:3801-3812.
18. Logsdon CD, Simeone DM, Binkley C, et al. Molecular profiling of pancreatic adenocarcinoma and chronic pancreatitis identifies multiple genes differentially regulated in pancreatic cancer. Cancer Res 2003;63:2649-2657.
19. Buchholz M, Braun M, Heidenblut A, et al. Transcriptome analysis of microdissected pancreatic intraepithelial neoplastic lesions. Oncogene 2005;24:6626-6636.
20. Yamazaki K, Yajima T, Nagao T, et al. Expression of transcription factor E2F-1 in pancreatic ductal carcinoma: An immunohistochemical study. Pathol Res Pract 2003;199:23-28.
21. Schneider G, Reichert M, Saur D, Hamacher R, Fritsch R, Schmid RM. HDAC3 is linked to cell cycle machinery in MiaPaCa2 cells by regulating transcription of skp2. Cell Prolif 2007;40:522-531.
22. Zhang L, Wang C. F-box protein Skp2: A novel transcriptional target of E2F. Oncogene 2006;25:2615-2627.
23. Salon C, Merdzhanova G, Brambilla C, Brambilla E, Gazzeri S, Eymin B. E2F-1, Skp2 and cyclin E oncoproteins are upregulated and directly correlated in high-grade neuroendocrine lung tumors. Oncogene 2007;26:6927-6936.
24. Yin X, Giap C, Lazo JS, Prochownik EV. Lowmolecular weight inhibitors of Myc-Max interaction and function. Oncogene 2003;22:6151-6159.
25. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006;7:606-619.
26. Knight ZA, Gonzalez B, Feldman ME, et al. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell 2006;125:733-747.
27. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 1995;378:785-789.
28. Pap M, Cooper GM. Role of glycogen synthase kinase-3 in the phosphatidylinositol 3-Kinase/Akt cell survival pathway. J Biol Chem 1998;273:19929-19932.
29. Sears R, Nuckolls F, Haura E, Taya Y, Tamai K, Nevins JR. Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev 2000;14:2501-2514.
30. Pulverer BJ, Fisher C, Vousden K, Littlewood T, Evan G, Woodgett JR. Site-specific modulation of c-Myc cotransformation by residues phosphorylated in vivo. Oncogene 1994;9:59-70.
31. Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR. Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature 2000;406:86-90.
32. Jope RS, Johnson GV. The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci 2004;29:95-102.
33. Ougolkov AV, Fernandez-Zapico ME, Savoy DN, Urrutia RA, Billadeau DD. Glycogen synthase kinase-3beta participates in nuclear factor kappaB-mediated gene transcription and cell survival in pancreatic cancer cells. Cancer Res 2005;65:2076-2081.
34. Ougolkov AV, Fernandez-Zapico ME, Bilim VN, Smyrk TC, Chari ST, Billadeau DD. Aberrant nuclear accumulation of glycogen synthase kinase-3beta in human pancreatic cancer: Association with kinase activity and tumor dedifferentiation. Clin Cancer Res 2006;12:5074-5081.
35. Wilson W IIIrd, Baldwin AS. Maintenance of constitutive IkappaB kinase activity by glycogen synthase kinase-3alpha/beta in pancreatic cancer. Cancer Res 2008;68:8156-8163.
36. Zhang Y, Wang Z, Li X, Magnuson NS. Pim kinase-dependent inhibition of c-Myc degradation. Oncogene 2008;27:4809-4819.
37. Nieminen AI, Partanen JI, Klefstrom J. c-Myc blazing a trail of death: Coupling of the mitochondrial and death receptor apoptosis pathways by c-Myc. Cell Cycle 2007;6:2464-2472.
38. Kotliarova S, Pastorino S, Kovell LC, et al. Glycogen synthase kinase-3 inhibition induces glioma cell death through c-MYC, nuclear factor-kappaB, and glucose regulation. Cancer Res 2008;68:6643-6651.
39. Leone G, DeGregori J, Sears R, Jakoi L, Nevins JR. Myc and Ras collaborate in inducing accumulation of active cyclin E/Cdk2 and E2F. Nature 1997;387:422-426.
40. Fernandez PC, Frank SR, Wang L, et al. Genomic targets of the human c-Myc protein. Genes Dev 2003;17:1115-1129.
41. Leung JY, Ehmann GL, Giangrande PH, Nevins JR. A role for Myc in facilitating transcription activation by E2F1. Oncogene 2008;27:4172-4179.
42. Polager S, Ginsberg D. E2F - At the crossroads of life and death. Trends Cell Biol 2008;18:528-535.
43. Chaussepied M, Ginsberg D. Transcriptional regulation of AKT activation by E2F. Mol Cell 2004;16:831-837.
44. Ladu S, Calvisi DF, Conner EA, Farina M, Factor VM, Thorgeirsson SS. E2F1 inhibits c-Myc-driven apoptosis via PIK3CA/Akt/mTOR and COX-2 in a mouse model of human liver cancer. Gastroenterology 2008;135:1322-1332.
45. Rodicker F, Stiewe T, Zimmermann S, Putzer BM. Therapeutic efficacy of E2F1 in pancreatic cancer correlates with TP73 induction. Cancer Res 2001;61:7052-7055.
46. Hallstrom TC, Nevins JR. Specificity in the activation and control of transcription factor E2F-dependent apoptosis. Proc Natl Acad Sci USA 2003;100:10848-10853.
47. Hallstrom TC, Mori S, Nevins JR. An E2F1-dependent gene expression program that determines the balance between proliferation and cell death. Cancer Cell 2008;13:11-22.