Combined mutation of Vhl and Trp53 causes renal cysts and tumours in mice

EMBO Molecular Medicine

Volumn 5, Issue 6, 2013, Pages 949-964

  Albers, Joachim ^a   Rajski, Michal ^a   Schönenberger, Désirée ^a   Harlander, Sabine ^a   Schraml, Peter ^b   von Teichman, Adriana ^b   Georgiev, Strahil ^c   Wild, Peter J ^a,b   Moch, Holger ^a,b   Krek, Wilhelm ^a,c   Frew, Ian J ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^c ETH ZURICH   (Switzerland)

Author keywords

CcRCC; Cyst; P53; VHL

Indexed keywords

CENTROMERE PROTEIN E; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MESSENGER RNA; MYC PROTEIN; PROTEIN MAD2; PROTEIN P53; VON HIPPEL LINDAU PROTEIN;

ANEUPLOIDY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARCINOGENESIS; CELL IMMORTALIZATION; CELL PROLIFERATION; CONTROLLED STUDY; EMBRYO; EUKARYOTIC FLAGELLUM; FIBROBLAST; GENE DELETION; GENE EXPRESSION; GENE INACTIVATION; HUMAN; HUMAN TISSUE; KIDNEY CARCINOMA; KIDNEY CYST; KIDNEY DYSPLASIA; KIDNEY EPITHELIUM; LOSS OF FUNCTION MUTATION; MALE; MOUSE; MOUSE EMBRYO; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; SEQUENCE ANALYSIS; TUMOR SUPPRESSOR GENE; UROTHELIUM; WESTERN BLOTTING; WILD TYPE;

ANEUPLOIDY; ANIMALS; CARCINOMA, RENAL CELL; CELL PROLIFERATION; CELLS, CULTURED; EPITHELIAL CELLS; FIBROBLASTS; HUMANS; KIDNEY; KIDNEY DISEASES, CYSTIC; KIDNEY NEOPLASMS; MICE; MICE, INBRED C57BL; MULTIPROTEIN COMPLEXES; PROTO-ONCOGENE PROTEINS C-MYC; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEIN P53; UROTHELIUM; VON HIPPEL-LINDAU TUMOR SUPPRESSOR PROTEIN;

EID: 84878697625     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.1002/emmm.201202231     Document Type: Article

References (52)

1. Bertout JA, Majmundar AJ, Gordan JD, Lam JC, Ditsworth D, Keith B, Brown EJ, Nathanson KL, Simon MC (2009) HIF2alpha inhibition promotes p53 pathway activity, tumor cell death, and radiation responses. Proc Natl Acad Sci USA 106: 14391-14396
2. Biju MP, Neumann AK, Bensinger SJ, Johnson RS, Turka LA, Haase VH (2004) Vhlh gene deletion induces Hif-1-mediated cell death in thymocytes. Mol Cell Biol 24: 9038-9047
3. Burds AA, Lutum AS, Sorger PK (2005) Generating chromosome instability through the simultaneous deletion of Mad2 and p53. Proc Natl Acad Sci USA 102: 11296-11301
4. Burrows AE, Smogorzewska A, Elledge SJ (2010) Polybromo-associated BRG1-associated factor components BRD7 and BAF180 are critical regulators of p53 required for induction of replicative senescence. Proc Natl Acad Sci USA 107: 14280-14285
5. Custer M, Lotscher M, Biber J, Murer H, Kaissling B (1994) Expression of Na-P(i) cotransport in rat kidney: localization by RT-PCR and immunohistochemistry. Am J Physiol 266: F767- F774
6. Dahinden C, Ingold B, Wild P, Boysen G, Luu VD, Montani M, Kristiansen G, Sulser T, Buhlmann P, Moch H, et al (2010) Mining tissue microarray data to uncover combinations of biomarker expression patterns that improve intermediate staging and grading of clear cell renal cell cancer. Clin Cancer Res 16: 88-98
7. Dalgliesh GL, Furge K, Greenman C, Chen L, Bignell G, Butler A, Davies H, Edkins S, Hardy C, Latimer C, et al (2010) Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 463: 360-363
8. Dickins RA, Hemann MT, Zilfou JT, Simpson DR, Ibarra I, Hannon GJ, Lowe SW (2005) Probing tumor phenotypes using stable and regulated synthetic microRNA precursors. Nat Genet 37: 1289-1295
9. Eble JN, Sauter G, Epstein JI, Sesterhehn IA (2004) World Health Organisation Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press
10. Esteban MA, Tran MG, Harten SK, Hill P, Castellanos MC, Chandra A, Raval R, O'Brien TS, Maxwell PH (2006) Regulation of E-cadherin expression by VHL and hypoxia-inducible factor. Cancer Res 66: 3567-3575
11. Frew IJ, Dickins RA, Cuddihy AR, Del Rosario M, Reinhard C, O'Connell MJ, Bowtell DD (2002) Normal p53 function in primary cells deficient for Siah genes. Mol Cell Biol 22: 8155-8164
12. Frew IJ, Krek W (2007) Multitasking by pVHL in tumour suppression. Curr Opin Cell Biol 19: 685-690
13. Frew IJ, Minola A, Georgiev S, Hitz M, Moch H, Richard S, Vortmeyer AO, Krek W (2008a) Combined VHLH and PTEN mutation causes genital tract cystadenoma and squamous metaplasia. Mol Cell Biol 28: 4536-4548
14. Frew IJ, Thoma CR, Georgiev S, Minola A, Hitz M, Montani M, Moch H, Krek W (2008b) pVHL and PTEN tumour suppressor proteins cooperatively suppress kidney cyst formation. EMBO J 27: 1747-1757
15. Gerstung M, Beisel C, Rechsteiner M, Wild P, Schraml P, Moch H, Beerenwinkel N (2012) Reliable detection of subclonal single-nucleotide variants in tumour cell populations. Nat Commun 3: 811
16. Guo G, Gui Y, Gao S, Tang A, Hu X, Huang Y, Jia W, Li Z, He M, Sun L, et al (2012) Frequent mutations of genes encoding ubiquitin-mediated proteolysis pathway components in clear cell renal cell carcinoma. Nat Genet 44: 17-19
17. Haase VH, Glickman JN, Socolovsky M, Jaenisch R (2001) Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor. Proc Natl Acad Sci USA 98: 1583-1588
18. Hergovich A, Lisztwan J, Barry R, Ballschmieter P, Krek W (2003) Regulation of microtubule stability by the von Hippel-Lindau tumour suppressor protein pVHL. Nat Cell Biol 5: 64-70
19. Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham MJ, et al (2012) The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature 485: 55-61
20. Hudes GR (2009) Targeting mTOR in renal cell carcinoma. Cancer 115: 2313-2320
21. Jonkers J, Meuwissen R, van der Gulden H, Peterse H, van der Valk M, Berns A (2001) Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat Genet 29: 418-425
22. Kaelin WG, Jr (2002) Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2: 673-682
23. Lubensky IA, Gnarra JR, Bertheau P, Walther MM, Linehan WM, Zhuang Z (1996) Allelic deletions of the VHL gene detected in multiple microscopic clear cell renal lesions in von Hippel-Lindau disease patients. Am J Pathol 149: 2089-2094
24. Luu VD, Boysen G, Struckmann K, Casagrande S, von Teichman A, Wild PJ, Sulser T, Schraml P, Moch H (2009) Loss of VHL and hypoxia provokes PAX2 up-regulation in clear cell renal cell carcinoma. Clin Cancer Res 15: 3297-3304
25. Mack FA, Patel JH, Biju MP, Haase VH, Simon MC (2005) Decreased growth of Vhl-/- fibrosarcomas is associated with elevated levels of cyclin kinase inhibitors p21 and p27. Mol Cell Biol 25: 4565-4578
26. Maher ER (2013) Genomics and epigenomics of renal cell carcinoma. Semin Cancer Biol 23: 10-17
27. Mandriota SJ, Turner KJ, Davies DR, Murray PG, Morgan NV, Sowter HM, Wykoff CC, Maher ER, Harris AL, Ratcliffe PJ, et al (2002) HIF activation identifies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephron. Cancer Cell 1: 459-468
28. Mao JH, Wu D, Perez-Losada J, Jiang T, Li Q, Neve RM, Gray JW, Cai WW, Balmain A (2007) Crosstalk between Aurora-A and p53: frequent deletion or downregulation of Aurora-A in tumors from p53 null mice. Cancer Cell 11: 161-173
29. Meraldi P, Draviam VM, Sorger PK (2004) Timing and checkpoints in the regulation of mitotic progression. Dev Cell 7: 45-60
30. Montani M, Heinimann K, von Teichman A, Rudolph T, Perren A, Moch H (2010) VHL-gene deletion in single renal tubular epithelial cells and renal tubular cysts: further evidence for a cyst-dependent progression pathway of clear cell renal carcinoma in von Hippel-Lindau disease. Am J Surg Pathol 34: 806-815
31. Monzon FA, Alvarez K, Peterson L, Truong L, Amato RJ, Hernandez-McClain J, Tannir N, Parwani AV, Jonasch E (2011) Chromosome 14q loss defines a molecular subtype of clear-cell renal cell carcinoma associated with poor prognosis. Mod Pathol 24: 1470-1479
32. Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S, Campisi J (2003) Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 5: 741-747
33. Pati D, Haddad BR, Haegele A, Thompson H, Kittrell FS, Shepard A, Montagna C, Zhang N, Ge G, Otta SK, et al (2004) Hormone-induced chromosomal instability in p53-null mammary epithelium. Cancer Res 64: 5608-5616
34. Pena-Llopis S, Vega-Rubin-de-Celis S, Liao A, Leng N, Pavia-Jimenez A, Wang S, Yamasaki T, Zhrebker L, Sivanand S, Spence P, et al (2012) BAP1 loss defines a new class of renal cell carcinoma. Nat Genet 44: 751-759
35. Pollard PJ, Spencer-Dene B, Shukla D, Howarth K, Nye E, El-Bahrawy M, Deheragoda M, Joannou M, McDonald S, Martin A, et al (2007) Targeted inactivation of fh1 causes proliferative renal cyst development and activation of the hypoxia pathway. Cancer Cell 11: 311-319
36. Rankin EB, Tomaszewski JE, Haase VH (2006) Renal cyst development in mice with conditional inactivation of the von Hippel-Lindau tumor suppressor. Cancer Res 66: 2576-2583
37. Roberts AM, Watson IR, Evans AJ, Foster DA, Irwin MS, Ohh M (2009) Suppression of hypoxia-inducible factor 2alpha restores p53 activity via Hdm2 and reverses chemoresistance of renal carcinoma cells. Cancer Res 69: 9056-9064
38. Roe JS, Kim H, Lee SM, Kim ST, Cho EJ, Youn HD (2006) p53 stabilization and transactivation by a von Hippel-Lindau protein. Mol Cell 22: 395-405
39. Stuart ET, Haffner R, Oren M, Gruss P (1995) Loss of p53 function through PAX-mediated transcriptional repression. EMBO J 14: 5638-5645
40. Tang SW, Chang WH, Su YC, Chen YC, Lai YH, Wu PT, Hsu CI, Lin WC, Lai MK, Lin JY (2009) MYC pathway is activated in clear cell renal cell carcinoma and essential for proliferation of clear cell renal cell carcinoma cells. Cancer Lett 273: 35-43
41. Thoma CR, Frew IJ, Hoerner CR, Montani M, Moch H, Krek W (2007) pVHL and GSK3beta are components of a primary cilium-maintenance signalling network. Nat Cell Biol 9: 588-595
42. Thoma CR, Toso A, Gutbrodt KL, Reggi SP, Frew IJ, Schraml P, Hergovich A, Moch H, Meraldi P, Krek W (2009) VHL loss causes spindle misorientation and chromosome instability. Nat Cell Biol 11: 994-1001
43. Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, Davies H, Jones D, Lin ML, Teague J, et al (2011) Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 469: 539-542
44. Vichai V, Kirtikara K (2006) Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc 1: 1112-1116
45. von Teichman A, Comperat E, Behnke S, Storz M, Moch H, Schraml P (2011) VHL mutations and dysregulation of pVHL- and PTEN-controlled pathways in multilocular cystic renal cell carcinoma. Mod Pathol 24: 571-578
46. Wagner CA, Loffing-Cueni D, Yan Q, Schulz N, Fakitsas P, Carrel M, Wang T, Verrey F, Geibel JP, Giebisch G, et al (2008) Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins. Am J Physiol Renal Physiol 294: F1373- F1380
47. Walther MM, Lubensky IA, Venzon D, Zbar B, Linehan WM (1995) Prevalence of microscopic lesions in grossly normal renal parenchyma from patients with von Hippel-Lindau disease, sporadic renal cell carcinoma and no renal disease: clinical implications. J Urol 154: 2010-2014; discussion 2014-2015
48. Welford SM, Dorie MJ, Li X, Haase VH, Giaccia AJ (2010) Renal oxygenation suppresses VHL loss-induced senescence that is caused by increased sensitivity to oxidative stress. Mol Cell Biol 30: 4595-4603
49. Wild PJ, Ikenberg K, Fuchs TJ, Rechsteiner M, Georgiev S, Fankhauser N, Noske A, Roessle M, Caduff R, Dellas A, et al (2012) p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans. EMBO Mol Med 4: 808-824
50. Xie P, Tian C, An L, Nie J, Lu K, Xing G, Zhang L, He F (2008) Histone methyltransferase protein SETD2 interacts with p53 and selectively regulates its downstream genes. Cell Signal 20: 1671-1678
51. Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, Grisanzio C, Signoretti S, Kaelin WG, Jr (2008) VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol 10: 361-369
52. Yuan J, Luo K, Zhang L, Cheville JC, Lou Z (2010) USP10 regulates p53 localization and stability by deubiquitinating p53. Cell 140: 384-396