DNA methylation is associated with downregulation of the organic cation transporter OCT1 (SLC22A1) in human hepatocellular carcinoma

Genome Medicine

Volumn 3, Issue 12, 2011, Pages

  Schaeffeler, Elke ^a   Hellerbrand, Claus ^b   Nies, Anne T ^a   Winter, Stefan ^a   Kruck, Stephan ^c   Hofmann, Ute ^a   van der Kuip, Heiko ^a   Zanger, Ulrich M ^a   Koepsell, Hermann ^d   Schwab, Matthias ^a,c  

^a DR MARGARETE FISCHER BOSCH INSTITUTE OF CLINICAL PHARMACOLOGY   (Germany)

^b UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^c UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^d UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ORGANIC CATION TRANSPORTER 1; ORGANIC CATION TRANSPORTER 2; ORGANIC CATION TRANSPORTER 3;

ARTICLE; CONTROLLED STUDY; DNA METHYLATION; DOWN REGULATION; GENE EXPRESSION; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LIVER CELL CARCINOMA; LIVER HISTOLOGY; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; MICROARRAY ANALYSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION;

EID: 84155173299     PISSN: None     EISSN: 1756994X     Source Type: Journal    
DOI: 10.1186/gm298     Document Type: Article

References (49)

1. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006, 6:674-687. 10.1038/nrc1934, 16929323.
2. Breuhahn K, Gores G, Schirmacher P. Strategies for hepatocellular carcinoma therapy and diagnostics: Lessons learned from high throughput and profiling approaches. Hepatology 2011, 53:2112-2121. 10.1002/hep.24313, 21433041.
3. Ciarimboli G. Organic cation transporters. Xenobiotica 2008, 38:936-971. 10.1080/00498250701882482, 18668435.
4. Koepsell H, Lips K, Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res 2007, 24:1227-1251. 10.1007/s11095-007-9254-z, 17473959.
5. Urban TJ, Giacomini KM. Organic cation transporters. Drug Transporters: Molecular Characterization and Role in Drug Disposition 2010, 11-33. Hoboken, NJ: John Wiley & Sons, You G, Morris ME.
6. Nies AT, Koepsell H, Damme K, Schwab M. Organic cation transporters (OCTs, MATEs), in vitro and in vivo evidence for the importance in drug therapy. Handb Exp Pharmacol 2011, 201:105-167. 10.1007/978-3-642-14541-4_3, 21103969.
7. Jonker JW, Schinkel AH. Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). J Pharmacol Exp Ther 2004, 308:2-9.
8. Hilgendorf C, Ahlin G, Seithel A, Artursson P, Ungell AL, Karlsson J. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab Dispos 2007, 35:1333-1340. 10.1124/dmd.107.014902, 17496207.
9. Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, Yamaoka Y, Tsunoda T, Furukawa Y, Nakamura Y. Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res 2001, 61:2129-2137.
10. Chang Q, Chen J, Beezhold KJ, Castranova V, Shi X, Chen F. JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma. Mol Cancer 2009, 8:64. 2732591, 19686584.
11. Park T, Yi SG, Shin YK, Lee S. Combining multiple microarrays in the presence of controlling variables. Bioinformatics 2006, 22:1682-1689. 10.1093/bioinformatics/btl183, 16705015.
12. Esteller M. Epigenetics in cancer. N Engl J Med 2008, 358:1148-1159. 10.1056/NEJMra072067, 18337604.
13. Melotte V, Lentjes MH, van den Bosch SM, Hellebrekers DM, de Hoon JP, Wouters KA, Daenen KL, Partouns-Hendriks IE, Stessels F, Louwagie J, Smits KM, Weijenberg MP, Sanduleanu S, Khalid-de Bakker CA, Oort FA, Meijer GA, Jonkers DM, Herman JG, de Bruine AP, van EM. N-Myc downstream-regulated gene 4 (NDRG4): a candidate tumor suppressor gene and potential biomarker for colorectal cancer. J Natl Cancer Inst 2009, 101:916-927. 10.1093/jnci/djp131, 19535783.
14. Wong IH, Lo YM, Zhang J, Liew CT, Ng MH, Wong N, Lai PB, Lau WY, Hjelm NM, Johnson PJ. Detection of aberrant p16 methylation in the plasma and serum of liver cancer patients. Cancer Res 1999, 59:71-73.
15. Brock MV, Hooker CM, Ota-Machida E, Han Y, Guo M, Ames S, Glockner S, Piantadosi S, Gabrielson E, Pridham G, Pelosky K, Belinsky SA, Yang SC, Baylin SB, Herman JG. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med 2008, 358:1118-1128. 10.1056/NEJMoa0706550, 18337602.
16. Aoki M, Terada T, Kajiwara M, Ogasawara K, Ikai I, Ogawa O, Katsura T, Inui K. Kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) is regulated by DNA methylation. Am J Physiol Renal Physiol 2008, 295:F165-F170. 10.1152/ajprenal.90257.2008, 18508876.
17. Amann T, Maegdefrau U, Hartmann A, Agaimy A, Marienhagen J, Weiss TS, Stoeltzing O, Warnecke C, Scholmerich J, Oefner PJ, Kreutz M, Bosserhoff AK, Hellerbrand C. GLUT1 expression is increased in hepatocellular carcinoma and promotes tumorigenesis. Am J Pathol 2009, 174:1544-1552. 10.2353/ajpath.2009.080596, 2671384, 19286567.
18. Hellerbrand C, Amann T, Schlegel J, Wild P, Bataille F, Spruss T, Hartmann A, Bosserhoff AK. The novel gene MIA2 acts as a tumour suppressor in hepatocellular carcinoma. Gut 2008, 57:243-251. 10.1136/gut.2007.129544, 17881540.
19. Kirovski G, Stevens AP, Czech B, Dettmer K, Weiss TS, Wild P, Hartmann A, Bosserhoff AK, Oefner PJ, Hellerbrand C. Down-regulation of methylthioadenosine phosphorylase (MTAP) induces progression of hepatocellular carcinoma via accumulation of 5'-deoxy-5'-methylthioadenosine (MTA). Am J Pathol 2011, 178:1145-1152. 10.1016/j.ajpath.2010.11.059, 21356366.
20. Nies AT, Koepsell H, Winter S, Burk O, Klein K, Kerb R, Zanger UM, Keppler D, Schwab M, Schaeffeler E. Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver. Hepatology 2009, 50:1227-1240. 10.1002/hep.23103, 19591196.
21. Kruck S, Bedke J, Hennenlotter J, Ohneseit PA, Kuehs U, Senger E, Sievert KD, Stenzl A. Activation of mTOR in renal cell carcinoma is due to increased phosphorylation rather than protein overexpression. Oncol Rep 2010, 23:159-163.
22. Theodorescu D, Broder SR, Boyd JC, Mills SE, Frierson HF. Cathepsin D and chromogranin A as predictors of long term disease specific survival after radical prostatectomy for localized carcinoma of the prostate. Cancer 1997, 80:2109-2119. 10.1002/(SICI)1097-0142(19971201)80:11<2109::AID-CNCR10>3.0.CO;2-2, 9392333.
23. Ehrich M, Nelson MR, Stanssens P, Zabeau M, Liloglou T, Xinarianos G, Cantor CR, Field JK, van den BD. Quantitative high-throughput analysis of DNA methylation patterns by base-specific cleavage and mass spectrometry. Proc Natl Acad Sci USA 2005, 102:15785-15790. 10.1073/pnas.0507816102, 1276092, 16243968.
24. Coolen MW, Statham AL, Gardiner-Garden M, Clark SJ. Genomic profiling of CpG methylation and allelic specificity using quantitative high-throughput mass spectrometry: critical evaluation and improvements. Nucleic Acids Res 2007, 35:e119. 10.1093/nar/gkm662, 2094090, 17855397.
25. Bock C, Walter J, Paulsen M, Lengauer T. CpG island mapping by epigenome prediction. PLoS Comput Biol 2007, 3:e110. 10.1371/journal.pcbi.0030110, 1892605, 17559301.
26. Lee S, Lee HJ, Kim JH, Lee HS, Jang JJ, Kang GH. Aberrant CpG island hypermethylation along multistep hepatocarcinogenesis. Am J Pathol 2003, 163:1371-1378. 10.1016/S0002-9440(10)63495-5, 1868296, 14507645.
27. Gao W, Kondo Y, Shen L, Shimizu Y, Sano T, Yamao K, Natsume A, Goto Y, Ito M, Murakami H, Osada H, Zhang J, Issa JP, Sekido Y. Variable DNA methylation patterns associated with progression of disease in hepatocellular carcinomas. Carcinogenesis 2008, 29:1901-1910. 10.1093/carcin/bgn170, 18632756.
28. Lambert MP, Paliwal A, Vaissiere T, Chemin I, Zoulim F, Tommasino M, Hainaut P, Sylla B, Scoazec JY, Tost J, Herceg Z. Aberrant DNA methylation distinguishes hepatocellular carcinoma associated with HBV and HCV infection and alcohol intake. J Hepatol 2011, 54:705-715. 10.1016/j.jhep.2010.07.027, 21146512.
29. Um TH, Kim H, Oh BK, Kim MS, Kim KS, Jung G, Park YN. Aberrant CpG island hypermethylation in dysplastic nodules and early HCC of hepatitis B virus-related human multistep hepatocarcinogenesis. J Hepatol 2011, 54:939-947. 10.1016/j.jhep.2010.08.021, 21145824.
30. Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, Chu X, Dahlin A, Evers R, Fischer V, Hillgren KM, Hoffmaster KA, Ishikawa T, Keppler D, Kim RB, Lee CA, Niemi M, Polli JW, Sugiyama Y, Swaan PW, Ware JA, Wright SH, Yee SW, Zamek-Gliszczynski MJ, Zhang L. Membrane transporters in drug development. Nat Rev Drug Discov 2010, 9:215-236. 10.1038/nrd3028, 20190787.
31. Lee JS, Chu IS, Heo J, Calvisi DF, Sun Z, Roskams T, Durnez A, Demetris AJ, Thorgeirsson SS. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling. Hepatology 2004, 40:667-676. 10.1002/hep.20375, 15349906.
32. Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, Mikaelyan A, Roberts LR, Demetris AJ, Sun Z, Nevens F, Roskams T, Thorgeirsson SS. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 2006, 12:410-416. 10.1038/nm1377, 16532004.
33. Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang HY, Jia H, Ye Q, Qin LX, Wauthier E, Reid LM, Minato H, Honda M, Kaneko S, Tang ZY, Wang XW. EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology 2009, 136:1012-1024. 10.1053/j.gastro.2008.12.004, 2828822, 19150350.
34. Hui L, Zatloukal K, Scheuch H, Stepniak E, Wagner EF. Proliferation of human HCC cells and chemically induced mouse liver cancers requires JNK1-dependent p21 downregulation. J Clin Invest 2008, 118:3943-3953. 10.1172/JCI37156, 2579707, 19033664.
35. Moribe T, Iizuka N, Miura T, Kimura N, Tamatsukuri S, Ishitsuka H, Hamamoto Y, Sakamoto K, Tamesa T, Oka M. Methylation of multiple genes as molecular markers for diagnosis of a small, well-differentiated hepatocellular carcinoma. Int J Cancer 2009, 125:388-397. 10.1002/ijc.24394, 19384946.
36. Lou C, Du Z, Yang B, Gao Y, Wang Y, Fang S. Aberrant DNA methylation profile of hepatocellular carcinoma and surgically resected margin. Cancer Sci 2009, 100:996-1004. 10.1111/j.1349-7006.2009.01138.x, 19385975.
37. Irizarry RA, Ladd-Acosta C, Wen B, Wu Z, Montano C, Onyango P, Cui H, Gabo K, Rongione M, Webster M, Ji H, Potash JB, Sabunciyan S, Feinberg AP. The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores. Nat Genet 2009, 41:178-186. 10.1038/ng.298, 2729128, 19151715.
38. Eckhardt F, Lewin J, Cortese R, Rakyan VK, Attwood J, Burger M, Burton J, Cox TV, Davies R, Down TA, Haefliger C, Horton R, Howe K, Jackson DK, Kunde J, Koenig C, Liddle J, Niblett D, Otto T, Pettett R, Seemann S, Thompson C, West T, Rogers J, Olek A, Berlin K, Beck S. DNA methylation profiling of human chromosomes 6, 20 and 22. Nat Genet 2006, 38:1378-1385. 10.1038/ng1909, 3082778, 17072317.
39. Brenet F, Moh M, Funk P, Feierstein E, Viale AJ, Socci ND, Scandura JM. DNA methylation of the first exon is tightly linked to transcriptional silencing. PLoS One 2011, 6:e14524. 10.1371/journal.pone.0014524, 3022582, 21267076.
40. Shu Y, Sheardown SA, Brown C, Owen RP, Zhang S, Castro RA, Ianculescu AG, Yue L, Lo JC, Burchard EG, Brett CM, Giacomini KM. Effect of genetic variation in the organic cation transporter 1 (OCT1) on metformin action. J Clin Invest 2007, 117:1422-1431. 10.1172/JCI30558, 1857259, 17476361.
41. More SS, Li S, Yee SW, Chen L, Xu Z, Jablons DM, Giacomini KM. Organic cation transporters modulate the uptake and cytotoxicity of picoplatin, a third-generation platinum analogue. Mol Cancer Ther 2010, 9:1058-1069. 10.1158/1535-7163.MCT-09-1084, 3258025, 20371711.
42. Gupta A, Lutsenko S. Human copper transporters: mechanism, role in human diseases and therapeutic potential. Future Med Chem 2009, 1:1125-1142. 10.4155/fmc.09.84, 2863355, 20454597.
43. Kacevska M, Ivanov M, Ingelman-Sundberg M. Perspectives on epigenetics and its relevance to adverse drug reactions. Clin Pharmacol Ther 2011, 89:902-907. 10.1038/clpt.2011.21, 21508940.
44. Baker EK, El-Osta A. MDR1, chemotherapy and chromatin remodeling. Cancer Biol Ther 2004, 3:819-824. 10.4161/cbt.3.9.1101, 15326379.
45. Nies AT, Herrmann E, Brom M, Keppler D. Vectorial transport of the plant alkaloid berberine by double-transfected cells expressing the human organic cation transporter 1 (OCT1, SLC22A1) and the efflux pump MDR1 P-glycoprotein (ABCB1). Naunyn Schmiedebergs Arch Pharmacol 2008, 376:449-461. 10.1007/s00210-007-0219-x, 18157518.
46. MethPrimer. , http://www.urogene.org/methprimer
47. Ehrich M, Turner J, Gibbs P, Lipton L, Giovanneti M, Cantor C, van den Boom D. Cytosine methylation profiling of cancer cell lines. Proc Natl Acad Sci USA 2008, 105:4844-4849. 10.1073/pnas.0712251105, 2290817, 18353987.
48. The R Project for Statistical Computing. , http://www.r-project.org
49. Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat 1979, 6:65-70.