Erythropoietin gene expression in renal carcinoma is considerably more frequent than paraneoplastic polycythemia

International Journal of Cancer

Volumn 121, Issue 11, 2007, Pages 2434-2442

  Wiesener, Michael S ^a,e   Münchenhagen, Philine ^b   Gläser, Markus ^b   Sobottka, Bettina A ^b   Knaup, Karl X ^a   Jozefowski, Katrin ^a   Jürgensen, Jan Steffen ^b   Roigas, Jan ^b   Warnecke, Christina ^a   Gröne, Hermann Josef ^c   Maxwell, Patrick H ^d   Willam, Carsten ^a   Eckardt, Kai Uwe ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

^b HUMBOLDT UNIVERSITY   (Germany)

^c UNIVERSITY OF HEIDELBERG   (Germany)

^d IMPERIAL COLLEGE LONDON   (United Kingdom)

^e UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

EPAS 1; Erythrocytosis; HIF 2 ; Oxygen; Transcription factor

Indexed keywords

ERYTHROPOIETIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; HYPOXIA INDUCIBLE FACTOR 2ALPHA; MESSENGER RNA;

ANGIOGENESIS; ARTICLE; AUTOCRINE EFFECT; CELL PROLIFERATION; CLEAR CELL CARCINOMA; EPO GENE; GENE; GENE EXPRESSION; HUMAN; HUMAN TISSUE; IN SITU HYBRIDIZATION; KIDNEY CARCINOMA; NUCLEOTIDE SEQUENCE; PARACRINE SIGNALING; PARANEOPLASTIC POLYCYTHEMIA; POLYCYTHEMIA; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; RIBONUCLEASE PROTECTION ASSAY; SIGNAL TRANSDUCTION; TUMOR CELL;

ADENOCARCINOMA, CLEAR CELL; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CARCINOMA, RENAL CELL; CELL LINE, TUMOR; ERYTHROPOIETIN; GENE EXPRESSION REGULATION, NEOPLASTIC; GERMANY; HUMANS; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; IMMUNOBLOTTING; IN SITU HYBRIDIZATION; KIDNEY NEOPLASMS; PARANEOPLASTIC SYNDROMES; POLYCYTHEMIA; PREVALENCE; RIBONUCLEASES; RNA, MESSENGER; SIGNAL TRANSDUCTION; TUMOR CELLS, CULTURED; UP-REGULATION;

EID: 35648992373     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.22961     Document Type: Article

References (69)

1. Fisher JW. Erythropoietin: physiology and pharmacology update. Exp Biol Med (Maywood) 2003;228:1-14.
2. Fandrey J. Oxygen-dependent and tissue-specific regulation of erythropoietin gene expression. Am J Physiol Regul Integr Comp Physiol 2004;286:R977-R988.
3. Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 1995;270:1230-7.
4. Wiesener MS, Turley H, Allen WE, Willam C, Eckardt KU, Talks KL, Wood SM, Gatter KC, Harris AL, Pugh CW, Ratcliffe PJ, Maxwell PH. Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-1α. Blood 1998;92:2260-8.
5. Wiesener MS, Jurgensen JS, Rosenberger C, Scholze CK, Horstrup JH, Warnecke C, Mandriota S, Bechmann I, Frei UA, Pugh CW, Ratcliffe PJ, Bachmann S, et al. Widespread hypoxia-inducible expression of HIF-2α in distinct cell populations of different organs. FASEB J 2003;17:271-3.
6. Rosenberger C, Mandriota S, Jurgensen JS, Wiesener MS, Horstrup JH, Frei U, Ratcliffe PJ, Maxwell PH, Bachmann S, Eckardt KU. Expression of hypoxia-inducible factor-1α and -2α in hypoxic and ischemic rat kidneys. J Am Soc Nephrol 2002;13:1721-32.
7. Stroka DM, Burkhardt T, Desbaillets I, Wenger RH, Neil DA, Bauer C, Gassmann M, Candinas D. HIF-1 is expressed in normoxic tissue and displays an organ-specific regulation under systemic hypoxia. FASEB J 2001;15:2445-53.
8. Warnecke C, Zaborowska Z, Kurreck J, Erdmann VA, Frei U, Wiesener M, Eckardt KU. Differentiating the functional role of hypoxia-inducible factor (HIF)-1α and HIF-2α (EPAS-1) by the use of RNA interference: erythropoietin is a HIF-2α target gene in Hep3B and Kelly cells. FASEB J 2004;18:1462-4.
9. Scortegagna M, Ding K, Zhang Q, Oktay Y, Bennett MJ, Bennett M, Shelton JM, Richardson JA, Moe O, Garcia JA. HIF-2α regulates murine hematopoietic development in an erythropoietin-dependent manner. Blood 2005;105:3133-40.
10. Scortegagna M, Morris MA, Oktay Y, Bennett M, Garcia JA. The HIF family member EPAS1/HIF-2α is required for normal hematopoiesis in mice. Blood 2003;102:1634-40.
11. Gruber M, Hu CJ, Johnson RS, Brown EJ, Keith B, Simon MC. Acute postnatal ablation of Hif-2α results in anemia. Proc Natl Acad Sci USA 2007;104:2301-6.
12. Schofield CJ, Ratcliffe PJ. Oxygen sensing by HIF hydroxylases. Nat Rev Mol Cell Biol 2004;5:343-54.
13. Pouyssegur J, Dayan F, Mazure NM. Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature 2006;441:437-43.
14. Bachmann S, Le Hir M, Eckardt KU. Co-localization of erythropoietin mRNA and ecto-5′-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin. J Histochem Cytochem 1993;41:335-41.
15. Maxwell PH, Osmond MK, Pugh CW, Heryet A, Nicholls LG, Tan CC, Doe BG, Ferguson DJ, Johnson MH, Ratcliffe PJ. Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int 1993;44:1149-62.
16. Maxwell PH, Ferguson DJ, Osmond MK, Pugh CW, Heryet A, Doe BG, Johnson MH, Ratcliffe PJ. Expression of a homologously recombined erythopoietin-SV40 T antigen fusion gene in mouse liver: evidence for erythropoietin production by Ito cells. Blood 1994;84:1823-30.
17. Eckardt KU, Pugh CW, Meier M, Tan CC, Ratcliffe PJ, Kurtz A Production of erythropoietin by liver cells in vivo and in vitro. Ann NY Acad. Sci 1994;718:50-60. discussion 61-3.
18. Semenza GL, Traystman MD, Gearhart JD, Antonarakis SE. Polycythemia in transgenic mice expressing the human erythropoietin gene. Proc Natl Acad Sci USA 1989;86:2301-5.
19. Semenza GL, Koury ST, Nejfelt MK, Gearhart JD, Antonarakis SE. Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice. Proc Natl Acad Sci USA 1991;88:8725-9.
20. Semenza GL, Dureza RC, Traystman MD, Gearhart JD, Antonarakis SE. Human erythropoietin gene expression in transgenic mice: multiple transcription initiation sites and cis-acting regulatory elements. Mol Cell Biol 1990;10:930-8.
21. Madan A, Lin C, Hatch SL, II, Curtin PT. Regulated basal, inducible, and tissue-specific human erythropoietin gene expression in transgenic mice requires multiple eis DNA sequences. Blood 1995;85:2735-41.
22. Noguchi Y, Goto T, Yufu Y, Uike N, Hasegawa Y, Fukuda T, Jimi A, Funakoshi A. Gene expression of erythropoietin in renal cell carcinoma. Intern Med 1999;38:991-4.
23. Da Silva JL, Lacombe C, Bruneval P, Casadevall N, Leporrier M, Camilleri JP, Bariety J, Tambourin P, Varet B. Tumor cells are the site of erythropoietin synthesis in human renal cancers associated with polycythemia. Blood 1990;75:577-82.
24. Clark D, Kersting R, Rojiani AM. Erythropoietin immunolocalization in renal cell carcinoma. Mod. Pathol 1998;11:24-8.
25. Hagiwara M, Chen IL, McGonigle R, Beckman B, Kasten FH, Fisher JW. Erythropoietin production in a primary culture of human renal carcinoma cells maintained in nude mice. Blood 1984;63:828-35.
26. Katsuoka Y, McGonigle R, Rege AB, Beckman B, Fisher JW. Erythropoietin production in human renal carcinoma cells passaged in nude mice and in tissue culture. Gann 1983;74:534-41.
27. Okabe T, Urabe A, Kato T, Chiba S, Takaku F. Production of erythropoietin-like activity by human renal and hepatic carcinomas in cell culture. Cancer 1985;55:1918-23.
28. Sytkowski AJ, Richie JP, Bicknell KA. New human renal carcinoma cell line established from a patient with erythrocytosis. Cancer Res 1983;43:1415-9.
29. Sherwood JB, Shouval D. Continuous production of erythropoietin by an established human renal carcinoma cell line: development of the cell line. Proc Natl Acad Sci USA 1986;83:165-9.
30. Toyama K, Fujiyama N, Suzuki H, Chen TP, Tamaoki N, Ueyama Y. Erythropoietin levels in the course of a patient with erythropoietin-producing renal cell carcinoma and transplantation of this tumor in nude mice. Blood 1979;54:245-53.
31. Shouval D, Anton M, Galun E, Sherwood JB. Erythropoietin-induced polycythemia in athymic mice following transplantation of a human renal carcinoma cell line. Cancer Res 1988;48:3430-4.
32. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999;399:271-5.
33. Wiesener MS, Munchenhagen PM, Berger I, Morgan NV, Roigas J, Schwiertz A, Jurgensen JS, Gruber G, Maxwell PH, Loning SA, Frei U, Maher ER, et al. Constitutive activation of hypoxia-inducible genes related to overexpression of hypoxia-inducible factor-1α in clear cell renal carcinomas. Cancer Res 2001;61:5215-22.
34. Turner KJ, Moore JW, Jones A, Taylor CF, Cuthbert-Heavens D, Han C, Leek RD, Gatter KC, Maxwell PH, Ratcliffe PJ, Cranston D, Harris AL. Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res 2002;62:2957-61.
35. Prchal JT Pathogenetic mechanisms of polycythemia vera and congenital polycythemic disorders. Semin Hematol 2001;38(Suppl 2):10-20.
36. Randi ML, Murgia A, Putti MC, Martella M, Casarin A, Opocher G, Fabris F. Low frequency of VHL gene mutations in young individuals with polycythemia and high serum erythropoietin. Haematologica 2005;90:689-91.
37. Pastore YD, Jelinek J, Ang S, Guan Y, Liu E, Jedlickova K, Krishnamurti L, Prchal JT. Mutations in the VHL gene in sporadic apparently congenital polycythemia. Blood 2003;101:1591-5.
38. Pastore Y, Jedlickova K, Guan Y, Liu E, Fahner J, Hasle H, Prchal JF, Prchal JT. Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia. Am J Hum Genet 2003;73:412-9.
39. Bento MC, Chang KT, Guan Y, Liu E, Caldas G, Gatti RA, Prchal JT. Congenital polycythemia with homozygous and heterozygous mutations of von Hippel-Lindau gene: five new Caucasian patients. Haematologica 2005;90:128-9.
40. Cario H, Schwarz K, Jorch N, Kyank U, Petrides PE, Schneider DT, Uhle R, Debatin KM, Kohne E. Mutations in the von Hippel-Lindau (VHL) tumor suppressor gene and VHL-haplotype analysis in patients with presumable congenital erythrocytosis. Haematologica 2005;90:19-24.
41. Ang SO, Chen H, Hirota K, Gordeuk VR, Jelinek J, Guan Y, Liu E, Sergueeva AI, Miasnikova GY, Mole D, Maxwell PH, Stockton DW, et al. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat Genet 2002;32:614-21.
42. Lee YS, Vortmeyer AO, Lubensky IA, Vogel TW, Ikejiri B, Ferlicot S, Benoit G, Giraud S, Oldfield EH, Linehan WM, Teh BT, Richard S, et al. Coexpression of erythropoietin and erythropoietin receptor in von Hippel-Lindau disease-associated renal cysts and renal cell carcinoma. Clin Cancer Res 2005;11:1059-64.
43. Vogel TW, Vortmeyer AO, Lubensky IA, Lee YS, Furuta M, Ikejiri B, Kim HJ, Lonser RR, Oldfield EH, Zhuang Z. Coexpression of erythropoietin and its receptor in endolymphatic sac tumors. J. Neurosurg 2005;103:284-8.
44. Gong K, Zhang N, Zhang Z, Na Y. Coexpression of erythopoietin and erythopoietin receptor in sporadic clear cell renal cell carcinoma. Cancer Biol Ther 2006;5:582-5.
45. Hardee ME, Arcasoy MO, Blackwell KL, Kirkpatrick JP, Dewhirst MW. Erythropoietin biology in cancer. Clin Cancer Res 2006;12:332-9.
46. Vaupel P, Mayer A, Briest S, Hockel M. Hypoxia in breast cancer: role of blood flow, oxygen diffusion distances, and anemia in the development of oxygen depletion. Adv Exp Med Biol 2005;566:333-42.
47. Henke M, Laszig R, Rube C, Schafer U, Haase KD, Schilcher B, Mose S, Beer KT, Burger U, Dougherty C, Frommhold H. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. Lancet 2003;362:1255-60.
48. Leyland-Jones B, Semiglazov V, Pawlicki M, Pienkowski T, Tjulandin S, Manikhas G, Makhson A, Roth A, Dodwell D, Baselga J, Biakhov M, Valuckas K, et al. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol 2005;23:5960-72.
49. Kovacs G, Akhtar M, Beckwith BJ, Bugert P, Cooper CS, Delahunt B, Eble JN, Fleming S, Ljungberg B, Medeiros LJ, Moch H, Reuter VE, et al. The Heidelberg classification of renal cell tumours. J Pathol 1997;183:131-3.
50. Skinnider BF, Folpe AL, Hennigar RA, Lim SD, Cohen C, Tamboli P, Young A, de Peralta-Venturina M, Amin MB. Distribution of cytokeratins and vimentin in adult renal neoplasms and normal renal tissue: potential utility of a cytokeratin antibody panel in the differential diagnosis of renal tumors. Am J Surg Pathol 2005;29:747-54.
51. Chu PG, Weiss LM. Keratin expression in human tissues and neoplasms. Histopathology 2002;40:403-39.
52. Maxwell PH, Dachs GU, Gleadle JM, Nicholls LG, Harris AL, Stratford IJ, Hankinson O, Pugh CW, Ratcliffe PJ. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA 1997;94:8104-9.
53. Maynard MA, Ohh M. Von Hippel-Lindau tumor suppressor protein and hypoxia-inducible factor in kidney cancer. Am J Nephrol 2004;24:1-13.
54. Maranchie JK, Vasselli JR, Riss J, Bonifacino JS, Linehan WM, Klausner RD. The contribution of VHL substrate binding and HIF1-α to the phenotype of VHL loss in renal cell carcinoma. Cancer Cell 2002;1:247-55.
55. Kondo K, Klco J, Nakamura E, Lechpammer M, Kaelin WG, Jr. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 2002;1:237-46.
56. Raval RR, Lau KW, Tran MG, Sowter HM, Mandriota SJ, Li JL, Pugh CW, Maxwell PH, Harris AL, Ratcliffe PJ. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol Cell Biol 2005;25:5675-86.
57. Yan Q, Bartz S, Mao M, Li L, Kaelin WG, Jr. The HIF2{α} N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo. Mol Cell Biol 2007;27:2092-102.
58. Motzer RJ, Bander NH, Nanus DM. Renal-cell carcinoma. N Engl J Med 1996;335:865-75.
59. Acs G, Acs P, Beckwith SM, Pitts RL, Clements E, Wong K, Verma A. Erythropoietin and erythropoietin receptor expression in human cancer. Cancer Res 2001;61:3561-5.
60. Dagnon K, Pacary E, Commo F, Antoine M, Bernaudin M, Bernaudin JF, Callard P. Expression of erythropoietin and erythropoietin receptor in non-small cell lung carcinomas. Clin Cancer Res 2005;11:993-9.
61. Vogel TW, Brouwers FM, Lubensky IA, Vortmeyer AO, Weil RJ, Walther MM, Oldfield EH, Linehan WM, Pacak K, Zhuang Z. Differential expression of erythropoietin and its receptor in von hippel-lindau-associated and multiple endocrine neoplasia type 2-associated pheochromocytomas. J Clin Endocrinol Metab 2005;90:3747-51.
62. Jelkmann W. Erythropoietin: structure, control of production, and function. Physiol Rev 1992;72:449-89.
63. Wiesener MS, Seyfarth M, Warnecke C, Jurgensen JS, Rosenberger C, Morgan NV, Maher ER, Frei U, Eckardt KU. Paraneoplastic erythrocytosis associated with an inactivating point mutation of the von Hippel-Lindau gene in a renal cell carcinoma. Blood 2002;99:3562-5.
64. Suzuki M, Takamizawa S, Nomaguchi K, Suzu S, Yamada M, Igarashi T, Sato I. Erythropoietin synthesis by tumour tissues in a patient with uterine myoma and erythrocytosis. Br J Haematol 2001;113:49-51.
65. Matsuo M, Koga S, Kanetake H, Ohtani H, Higami Y, Shimokawa I, Watanabe J EPO-producing gastric carcinoma in a hemodialysis patient. Am J Kidney Dis 2003;42:E3-E4.
66. Kaito K, Otsubo H, Usui N, Kobayashi M. Secondary polycythemia as a paraneoplastic syndrome of testicular seminoma. Ann Hematol 2004;83:55-7.
67. Cheng TI, Tsou MH, Yang PS, Sung SM, Chuang VP, Sung JL. Dermatomyositis and erythrocytosis associated with hepatocellular carcinoma. J Gastroenterol Hepatol 2002;17:1239-40.
68. Wang LY, Shih LY, Chen SH, Liu HC, Chai IJ, Liang DC. Neuroblastoma with expression of erythropoietin resulting in erythrocytosis. J Pediatr Hematol Oncol 2003;25:649-50.
69. Westenfelder C. Unexpected renal actions of erythropoietin. Exp Nephrol 2002;10:294-8.