Inactivation of Brca2 cooperates with Trp53R172H to induce invasive pancreatic ductal adenocarcinomas in mice: A mouse model of familial pancreatic cancer

Cancer Biology and Therapy

Volumn 11, Issue 11, 2011, Pages 959-968

  Feldmann, Georg ^a,b   Karikari, Collins ^b   Dal Molin, Marco ^b   Duringer, Stephanie ^c   Volkmann, Petra ^c   Bartsch, Detlef K ^c   Bisht, Savita ^a,b   Koorstra, Jan Bart ^b   Brossart, Peter ^a   Maitra, Anirban ^b   Fendrich, Volker ^c  

^a UNIVERSITY OF BONN   (Germany)

^b JOHNS HOPKINS UNIVERSITY   (United States)

^c PHILIPPS UNIVERSITY MARBURG   (Germany)

Author keywords

Brca2; DNA damage; Familial pancreatic cancer; Genetically engineered model; mPanIN; p53; Pancreatic ductal adenocarcinoma

Indexed keywords

BRCA2 PROTEIN; DNA; PROTEIN P53; TRANSCRIPTION FACTOR PDX 1; TRP53 PROTEIN; UNCLASSIFIED DRUG;

ALLELE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INVASION; CANCER MORTALITY; CARCINOGENESIS; CONTROLLED STUDY; DNA DAMAGE; EPITHELIUM; GENE DELETION; GENE INACTIVATION; GENE MUTATION; HISTOPATHOLOGY; METASTASIS; MOUSE; NONHUMAN; PANCREAS ADENOCARCINOMA; PANCREAS SECRETION; PREVALENCE; PROTEIN FUNCTION;

ADENOCARCINOMA; ANIMALS; BRCA2 PROTEIN; CARCINOMA IN SITU; CARCINOMA, PANCREATIC DUCTAL; DNA DAMAGE; GENE KNOCKDOWN TECHNIQUES; GENETIC ASSOCIATION STUDIES; HEDGEHOG PROTEINS; KAPLAN-MEIER ESTIMATE; LIVER NEOPLASMS; MICE; NEOPLASM TRANSPLANTATION; NEOPLASMS, EXPERIMENTAL; PANCREAS; PANCREATIC NEOPLASMS; PROTO-ONCOGENE PROTEINS P21(RAS); SPLENIC NEOPLASMS; TUMOR SUPPRESSOR PROTEIN P53;

EID: 79957828268     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.11.11.15534     Document Type: Article

References (44)

1. Feldmann G, Maitra A. Molecular genetics of pancreatic ductal adenocarcinomas and recent implications for translational efforts. J Mol Diagn 2008; 10:111-22. (Pubitemid 351428392)
2. Hruban RH, Adsay NV, Albores-Saavedra J, Anver MR, Biankin AV, Boivin GP, et al. Pathology of genetically engineered mouse models of pancreatic exocrine cancer: consensus report and recommendations. Cancer Res 2006; 66:95-106. (Pubitemid 43166014)
3. Tuveson DA, Hingorani SR. Ductal pancreatic cancer in humans and mice. Cold Spring Harb Symp Quant Biol 2005; 70:65-72. (Pubitemid 44124857)
4. Olive KP, Tuveson DA. The use of targeted mouse models for preclinical testing of novel cancer therapeutics. Clin Cancer Res 2006; 12:5277-87. (Pubitemid 44497240)
5. Hruban RH, Klein AP, Eshleman JR, Axilbund JE, Goggins M. Familial pancreatic cancer: from genes to improved patient care. Expert Rev Gastroenterol Hepatol 2007; 1:81-8.
6. Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 2009; 324:217.
7. Couch FJ, Johnson MR, Rabe KG, Brune K, de Andrade M, Goggins M, et al. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev 2007; 16:342-6. (Pubitemid 46383356)
8. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui- Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009; 361:123-34.
9. Villarroel MC, Rajesh Kumar NV, Garrido-Laguna I, De Jesus-Acosta A, Jones S, Maitra A, et al. Personalizing cancer treatment in the age of global genomic analyses: PALB2 gene mutations and the response to DNA damaging agents in pancreatic cancer. Mol Cancer Ther 2011; 10:3-8.
10. Goggins M, Hruban RH, Kern SE. BRCA2 is inactivated late in the development of pancreatic intraepithelial neoplasia: evidence and implications. Am J Pathol 2000; 156:1767-71. (Pubitemid 30646713)
11. Boulton SJ. Cellular functions of the BRCA tumoursuppressor proteins. Biochem Soc Trans 2006; 34:633-45. (Pubitemid 44796392)
12. Hutchinson L. Targeted therapies: PARP inhibitor olaparib is safe and effective in patients with BRCA1 and BRCA2 mutations. Nat Rev Clin Oncol 7:549.
13. Hruban RH, Klimstra DS, Pitman MB. Tumors of the pancreas. Washington DC: American Registry of Pathology 2006.
14. Fillingham J, Keogh MC, Krogan NJ. GammaH2AX and its role in DNA double-strand break repair. Biochem Cell Biol 2006; 84:568-77. (Pubitemid 44703660)
15. Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005; 434:864-70. (Pubitemid 40558993)
16. Maitra A, Hruban RH. Pancreatic cancer. Annu Rev Pathol 2008; 3:157-88. (Pubitemid 351488279)
17. Hingorani SR, Petricoin EF, Maitra A, Rajapakse V, King C, Jacobetz MA, et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 2003; 4:437-50. (Pubitemid 38050041)
18. Aguirre AJ, Bardeesy N, Sinha M, Lopez L, Tuveson DA, Horner J, et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev 2003; 17:3112-26. (Pubitemid 38040774)
19. Hidalgo M, Maitra A. The hedgehog pathway and pancreatic cancer. N Engl J Med 2009; 361:2094-6.
20. Berman DM, Karhadkar SS, Maitra A, Montes De Oca R, Gerstenblith MR, Briggs K, et al. Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 2003; 425:846-51. (Pubitemid 37351469)
21. Shi C, Hruban RH, Klein AP. Familial pancreatic cancer. Arch Pathol Lab Med 2009; 133:365-74.
22. Hruban RH, Canto MI, Griffin C, Kern SE, Klein AP, Laheru D, et al. Treatment of familial pancreatic cancer and its precursors. Curr Treat Options Gastroenterol 2005; 8:365-75. (Pubitemid 41684198)
23. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434:917-21. (Pubitemid 40559006)
24. Merritt AJ, Allen TD, Potten CS, Hickman JA. Apoptosis in small intestinal epithelial from p53- null mice: evidence for a delayed, p53-independent G2/M-associated cell death after gamma-irradiation. Oncogene 1997; 14:2759-66. (Pubitemid 27313407)
25. Vakifahmetoglu H, Olsson M, Tamm C, Heidari N, Orrenius S, Zhivotovsky B. DNA damage induces two distinct modes of cell death in ovarian carcinomas. Cell Death Differ 2008; 15:555-66. (Pubitemid 351267306)
26. Goggins M, Schutte M, Lu J, Moskaluk CA, Weinstein CL, Petersen GM, et al. Germline BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer Res 1996; 56:5360-4. (Pubitemid 27011364)
27. Olive KP, Tuveson DA, Ruhe ZC, Yin B, Willis NA, Bronson RT, et al. Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome. Cell 2004; 119:847-60. (Pubitemid 40017690)
28. Jackson EL, Olive KP, Tuveson DA, Bronson R, Crowley D, Brown M, et al. The differential effects of mutant p53 alleles on advanced murine lung cancer. Cancer Res 2005; 65:10280-8. (Pubitemid 41743720)
29. Hingorani SR, Wang L, Multani AS, Combs C, Deramaudt TB, Hruban RH, et al. Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 2005; 7:469-83. (Pubitemid 40719130)
30. Bardeesy N, Aguirre AJ, Chu GC, Cheng KH, Lopez LV, Hezel AF, et al. Both p16(Ink4a) and the p19(Arf )- p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse. Proc Natl Acad Sci USA 2006; 103:5947-52.
31. Habbe N, Shi G, Meguid RA, Fendrich V, Esni F, Chen H, et al. Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc Natl Acad Sci USA 2008; 105:18913-8.
32. Gidekel Friedlander SY, Chu GC, Snyder EL, Girnius N, Dibelius G, Crowley D, et al. Context-dependent transformation of adult pancreatic cells by oncogenic K-Ras. Cancer Cell 2009; 16:379-89.
33. Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev 2006; 20:3130-46. (Pubitemid 44790628)
34. Izeradjene K, Combs C, Best M, Gopinathan A, Wagner A, Grady WM, et al. Kras(G12D) and Smad4/ Dpc4 haploinsufficiency cooperate to induce mucinous cystic neoplasms and invasive adenocarcinoma of the pancreas. Cancer Cell 2007; 11:229-43. (Pubitemid 46349845)
35. Pasca di Magliano M, Sekine S, Ermilov A, Ferris J, Dlugosz AA, Hebrok M. Hedgehog/Ras interactions regulate early stages of pancreatic cancer. Genes Dev 2006; 20:3161-73. (Pubitemid 44790630)
36. Jones S, Zhang X, Parsons DW, Lin JC, Leary RJ, Angenendt P, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321:1801-6.
37. Calhoun ES, Jones JB, Ashfaq R, Adsay V, Baker SJ, Valentine V, et al. BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets. Am J Pathol 2003; 163:1255-60. (Pubitemid 37175075)
38. Skoulidis F, Cassidy LD, Pisupati V, Jonasson JG, Bjarnason H, Eyfjord JE, et al. Germline Brca2 heterozygosity promotes Kras(G12D) - driven carcinogenesis in a murine model of familial pancreatic cancer. Cancer Cell 2010; 18:499-509.
39. Rowley M, Ohashi A, Mondal G, Mills L, Yang L, Zhang L, et al. Inactivation of Brca2 promotes Trp53- associated but inhibits KrasG12D-dependent pancreatic cancer development in mice. Gastroenterology 2011; 140:1303-13. DOI: 10.1053/j.gastro.2010.12.039.
40. Negrini S, Gorgoulis VG, Halazonetis TD. Genomic instability - an evolving hallmark of cancer. Nat Rev Mol Cell Biol 11:220-8; (DOI: nrm2858 [pii]).
41. Bartek J, Bartkova J, Lukas J. DNA damage signalling guards against activated oncogenes and tumour progression. Oncogene 2007; 26:7773-9. (Pubitemid 350242463)
42. Jonkers J, Meuwissen R, van der Gulden H, Peterse H, van der Valk M, Berns A. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat Genet 2001; 29:418-25. (Pubitemid 34326692)
43. Fendrich V, Chen NM, Neef M, Waldmann J, Buchholz M, Feldmann G, et al. The angiotensin-Iconverting enzyme inhibitor enalapril and aspirin delay progression of pancreatic intraepithelial neoplasia and cancer formation in a genetically engineered mouse model of pancreatic cancer. Gut 2009; 59:630-7.
44. Slape C, Liu LY, Beachy S, Aplan PD. Leukemic transformation in mice expressing a NUP98-HOXD13 transgene is accompanied by spontaneous mutations in Nras, Kras and Cbl. Blood 2008; 112:2017-9.