Epigenetic regulation of ABCB1 transporter expression and function

Current Pharmacogenomics and Personalized Medicine

Volumn 8, Issue 3, 2010, Pages 218-231

  Reed, Kerry ^a,b   Parissenti, Amadeo M ^a,b,c,d  

^a LAURENTIAN UNIVERSITY   (Canada)

^b SUDBURY REGIONAL HOSPITAL   (Canada)

^c NORTHERN ONTARIO SCHOOL OF MEDICINE   (Canada)

^d UNIVERSITY OF OTTAWA   (Canada)

Author keywords

ABCB1; Chemotherapy; DNA methylation; Drug resistance; Epigenetics; Histone acetylation; MDR1; P glycoprotein

Indexed keywords

DNA METHYLTRANSFERASE; HISTONE; MULTIDRUG RESISTANCE PROTEIN 1;

ACETYLATION; ARTICLE; CANCER CHEMOTHERAPY; CANCER RESISTANCE; CPG ISLAND; DNA METHYLATION; EPIGENETICS; GENETIC REGULATION; HUMAN; NONHUMAN; PATIENT MONITORING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; TRANSCRIPTION INITIATION SITE;

EID: 78649287537     PISSN: 18756921     EISSN: 18756913     Source Type: Journal    
DOI: 10.2174/187569210792246317     Document Type: Article

References (139)

1. Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971; 68(4): 820-3.
2. Gottesman MM, Hrycyna CA, Schoenlein PV, et al. Genetic analysis of the multidrug transporter. Annu Rev Genet 1995; 29: 607-49.
3. Gama-Sosa MA, Slagel VA, Trewyn RW, et al. The 5 methylcytosine content of DNA from human tumors. Nucleic Acids Res 1983; 11(19): 6883-94.
4. Esteller M. Aberrant DNA methylation as a cancer-inducing mechanism. Annu Rev Pharmacol Toxicol 2005; 45: 629-56.
5. Plass C. Cancer epigenomics. Hum Mol Genet 2002; 11(20): 2479-88.
6. Glasspool RM, Teodoridis JM, Brown R. Epigenetics as a mechanism driving polygenic clinical drug resistance. Br J Cancer 2006; 94(8): 1087-92.
7. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 1976; 455(1): 152-62.
8. Scotto KW. Transcriptional regulation of ABC drug transporters. Oncogene 2003; 22(47): 7496-511.
9. Kovalchuk O, Filkowski J, Meservy J, et al. Involvement of microRNA 451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther 2008; 7(7): 2152-9.
10. Wang D, Johnson AD, Papp AC, et al. Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C>T affects mRNA stability. Pharmacogenet Genomics 2005; 15(10): 693-704.
11. Mickley LA, Lee JS, Weng Z, et al. Genetic polymorphism in MDR-1: a tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors. Blood 1998; 91(5): 1749-56.
12. Lee CH, Bradley G, Ling V. Increased P-glycoprotein messenger RNA stability in rat liver tumors in vivo. J Cell Physiol 1998; 177(1): 1-12.
13. Chen GK, Lacayo NJ, Duran GE, et al. Preferential expression of a mutant allele of the amplified MDR1 (ABCB1) gene in drugresistant variants of a human sarcoma. Genes Chromosomes Cancer 2002; 34(4): 372-83.
14. Buys TP, Chari R, Lee EH, et al. Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cells. Genes Chromosomes Cancer 2007; 46(12): 1069-79.
15. de Silva MG, Kantharidis P, Scherer SW, et al. Physical mapping of a tandem duplication on the long arm of chromosome 7 associated with a multidrug resistant phenotype. Cancer Genet Cytogenet 1999; 110(1): 28-33.
16. Kitada K, Yamasaki T. The MDR1/ABCB1 regional amplification in large inverted repeats with asymmetric sequences and microhomologies at the junction sites. Cancer Genet Cytogenet 2007; 178(2): 120-7.
17. Wang YC, Juric D, Francisco B, et al. Regional activation of chromosomal arm 7q with and without gene amplification in taxane selected human ovarian cancer cell lines. Genes Chromosomes Cancer 2006; 45(4): 365-74.
18. Yabuki N, Sakata K, Yamasaki T, et al. Gene amplification and expression in lung cancer cells with acquired paclitaxel resistance. Cancer Genet Cytogenet 2007; 173(1): 1-9.
19. Mickley LA, Spengler BA, Knutsen TA, et al. Gene rearrangement: a novel mechanism for MDR-1 gene activation. J Clin Invest 1997; 99(8): 1947-57.
20. Strathdee G, Sim A, Brown R. Control of gene expression by CpG island methylation in normal cells. Biochem Soc Trans 2004; 32(Pt 6): 913-5.
21. Lander ES, Linton LM, Birren B, et al. Initial sequencing and analysis of the human genome. Nature 2001; 409(6822): 860-921.
22. Zhang X, Yazaki J, Sundaresan A, et al. Genome-wide highresolution mapping and functional analysis of DNA methylation in arabidopsis. Cell 2006; 126(6): 1189-201.
23. Weber M, Hellmann I, Stadler MB, et al. Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome. Nat Genet 2007; 39(4): 457-66.
24. Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol 1987; 196(2): 261-82.
25. Shen L, Kondo Y, Guo Y, et al. Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genet 2007; 3(10): 2023-36.
26. Luczak MW, Jagodzinski PP. The role of DNA methylation in cancer development. Folia Histochem Cytobiol 2006; 44(3): 143-54.
27. Esteller M, Corn PG, Baylin SB, et al. A gene hypermethylation profile of human cancer. Cancer Res 2001; 61(8): 3225-9.
28. Costello JF, Fruhwald MC, Smiraglia DJ, et al. Aberrant CpGisland methylation has non-random and tumour-type-specific patterns. Nat Genet 2000; 24(2): 132-8.
29. Narayan A, Ji W, Zhang XY, et al. Hypomethylation of pericentromeric DNA in breast adenocarcinomas. Int J Cancer 1998; 77(6): 833-8.
30. Qu G, Dubeau L, Narayan A, et al. Satellite DNA hypomethylation vs. overall genomic hypomethylation in ovarian epithelial tumors of different malignant potential. Mutat Res 1999; 423(1-2): 91-101.
31. Kim YI, Giuliano A, Hatch KD, et al. Global DNA hypomethylation increases progressively in cervical dysplasia and carcinoma. Cancer 1994; 74(3): 893-9.
32. Bestor T, Laudano A, Mattaliano R, et al. Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases. J Mol Biol 1988; 203(4): 971-83.
33. Vilkaitis G, Suetake I, Klimasauskas S, et al. Processive methylation of hemimethylated CpG sites by mouse Dnmt1 DNA methyltransferase. J Biol Chem 2005; 280(1): 64-72.
34. Leonhardt H, Page AW, Weier HU, et al. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 1992; 71(5): 865-73.
35. Schermelleh L, Haemmer A, Spada F, et al. Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Res 2007; 35(13): 4301-12.
36. Okano M, Bell DW, Haber DA, et al. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 1999; 99(3): 247-57.
37. Li E, Bestor TH, Jaenisch R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 1992; 69(6): 915-26.
38. Jia D, Jurkowska RZ, Zhang X, et al. Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature 2007; 449(7159): 248-51.
39. Cao YX, Jean JC, Williams MC. Cytosine methylation of an Sp1 site contributes to organ-specific and cell-specific regulation of expression of the lung epithelial gene t1alpha. Biochem J 2000; 350(Pt 3): 883-90.
40. Kitazawa S, Kitazawa R, Maeda S. Transcriptional regulation of rat cyclin D1 gene by CpG methylation status in promoter region. J Biol Chem 1999; 274(40): 28787-93.
41. Ballestar E, Esteller M. Methyl-CpG-binding proteins in cancer: blaming the DNA methylation messenger. Biochem Cell Biol 2005; 83(3): 374-84.
42. Ballestar E, Wolffe AP. Methyl-CpG-binding proteins. Targeting specific gene repression. Eur J Biochem 2001; 268(1): 1-6.
43. Zhang Y, Ng HH, Erdjument-Bromage H, et al. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev 1999; 13(15): 1924-35.
44. Ng HH, Zhang Y, Hendrich B, et al. MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex. Nat Genet 1999; 23(1): 58-61.
45. Santos-Rosa H, Caldas C. Chromatin modifier enzymes, the histone code and cancer. Eur J Cancer 2005; 41(16): 2381-402.
46. Shilatifard A. Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem 2006; 75: 243-69.
47. Ballestar E, Esteller M. The epigenetic breakdown of cancer cells: from DNA methylation to histone modifications. Prog Mol Subcell Biol 2005; 38: 169-81.
48. Nishida H, Suzuki T, Kondo S, et al. Histone H3 acetylated at lysine 9 in promoter is associated with low nucleosome density in the vicinity of transcription start site in human cell. Chromosome Res 2006; 14(2): 203-11.
49. Baker EK, El-Osta A. The rise of DNA methylation and the importance of chromatin on multidrug resistance in cancer. Exp Cell Res 2003; 290(2): 177-94.
50. Lehnert M. Clinical multidrug resistance in cancer: a multifactorial problem. Eur J Cancer 1996; 32A(6): 912-20.
51. Germann UA, Chambers TC. Molecular analysis of the multidrug transporter, P-glycoprotein. Cytotechnology 1998; 27(1-3): 31-60.
52. Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, et al. P-glycoprotein: from genomics to mechanism. Oncogene 2003; 22(47): 7468-85.
53. Thiebaut F, Tsuruo T, Hamada H, et al. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 1987; 84(21): 7735-8.
54. Fojo AT, Ueda K, Slamon DJ, et al. Expression of a multidrugresistance gene in human tumors and tissues. Proc Natl Acad Sci USA 1987; 84(1): 265-9.
55. Johnsson A, Vallon-Christensson J, Strand C, et al. Gene expression profiling in chemoresistant variants of three cell lines of different origin. Anticancer Res 2005; 25(4): 2661-8.
56. Kars MD, Iseri OD, Gunduz U, et al. Development of rational in vitro models for drug resistance in breast cancer and modulation of MDR by selected compounds. Anticancer Res 2006; 26(6B): 4559-68.
57. Guo B, Villeneuve DJ, Hembruff SL, et al. Cross-resistance studies of isogenic drug-resistant breast tumor cell lines support recent clinical evidence suggesting that sensitivity to paclitaxel may be strongly compromised by prior doxorubicin exposure. Breast Cancer Res Treat 2004; 85(1): 31-51.
58. Mealey KL, Barhoumi R, Burghardt RC, et al. Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells. Antimicrob Agents Chemother 2002; 46(3): 755-61.
59. Chuthapisith S, Layfield R, Kerr ID, et al. Proteomic profiling of MCF-7 breast cancer cells with chemoresistance to different types of anti-cancer drugs. Int J Oncol 2007; 30(6): 1545-51.
60. Duan Z, Lamendola DE, Duan Y, et al. Description of paclitaxel resistance-associated genes in ovarian and breast cancer cell lines. Cancer Chemother Pharmacol 2005; 55(3): 277-85.
61. Hembruff SL, Laberge ML, Villeneuve DJ, et al. Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance. BMC Cancer 2008; 8: 318.
62. Takeda M, Mizokami A, Mamiya K, et al. The establishment of two paclitaxel-resistant prostate cancer cell lines and the mechanisms of paclitaxel resistance with two cell lines. Prostate 2007; 67(9): 955-67.
63. Szakacs G, Annereau JP, Lababidi S, et al. Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell 2004; 6(2): 129-37.
64. Leith CP, Kopecky KJ, Chen IM, et al. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood 1999; 94(3): 1086-99.
65. List AF, Kopecky KJ, Willman CL, et al. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood 2001; 98(12): 3212-20.
66. Marie JP, Legrand O. MDR1/P-GP expression as a prognostic factor in acute leukemias. Adv Exp Med Biol 1999; 457: 1-9.
67. Goldstein LJ, Galski H, Fojo A, et al. Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 1989; 81(2): 116-24.
68. Goldstein LJ. MDR1 gene expression in solid tumours. Eur J Cancer 1996; 32A(6): 1039-50.
69. Kanamaru H, Kakehi Y, Yoshida O, et al. MDR1 RNA levels in human renal cell carcinomas: correlation with grade and prediction of reversal of doxorubicin resistance by quinidine in tumor explants. J Natl Cancer Inst 1989; 81(11): 844-9.
70. Kakehi Y, Kanamaru H, Yoshida O, et al. Measurement of multidrug-resistance messenger RNA in urogenital cancers; elevated expression in renal cell carcinoma is associated with intrinsic drug resistance. J Urol 1988; 139(4): 862-5.
71. Tada Y, Wada M, Kuroiwa K, et al. MDR1 gene overexpression and altered degree of methylation at the promoter region in bladder cancer during chemotherapeutic treatment. Clin Cancer Res 2000; 6(12): 4618-27.
72. Mechetner E, Kyshtoobayeva A, Zonis S, et al. Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correlate with in vitro resistance to taxol and doxorubicin. Clin Cancer Res 1998; 4(2): 389-98.
73. Wang CS, LaRue H, Fortin A, et al. mdr1 mRNA expression by RT-PCR in patients with primary breast cancer submitted to neoadjuvant therapy. Breast Cancer Res Treat 1997; 45(1): 63-74.
74. Punyammalee B, Manoromana S, Purisa W, et al. Association of mdr1 gene expression with other prognostic factors and clinical outcome in human breast cancer. J Med Assoc Thai 1997; 80(Suppl 1): S162-S173.
75. Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 1993; 62: 385-427.
76. Raguz S, Tamburo De BM, Tripuraneni G, et al. Activation of the MDR1 upstream promoter in breast carcinoma as a surrogate for metastatic invasion. Clin Cancer Res 2004; 10(8): 2776-83.
77. Raguz S, Randle RA, Sharpe ER, et al. Production of Pglycoprotein from the MDR1 upstream promoter is insufficient to affect the response to first-line chemotherapy in advanced breast cancer. Int J Cancer 2008; 122(5): 1058-67.
78. Charpin C, Vielh P, Duffaud F, et al. Quantitative immunocytochemical assays of P-glycoprotein in breast carcinomas: correlation to messenger RNA expression and to immunohistochemical prognostic indicators. J Natl Cancer Inst 1994; 86(20): 1539-45.
79. Gao P, Yang X, Xue YW, et al. Promoter methylation of glutathione S-transferase pi1 and multidrug resistance gene 1 in bronchioloalveolar carcinoma and its correlation with DNA methyltransferase 1 expression. Cancer 2009; 115(14): 3222-32.
80. Aszalos A. Drug-drug interactions affected by the transporter protein, P-glycoprotein (ABCB1, MDR1) II. Clinical aspects. Drug Discov Today 2007; 12(19-20): 838-43.
81. Nobili S, Landini I, Giglioni B, et al. Pharmacological strategies for overcoming multidrug resistance. Curr Drug Targets 2006; 7(7): 861-79.
82. Kantharidis P, El-Osta S, Silva M, et al. Regulation of MDR1 gene expression: emerging concepts. Drug Resist Updat 2000; 3(2): 99-108.
83. Lancet JE, Baer MR, Duran GE, et al. A phase I trial of continuous infusion of the multidrug resistance inhibitor zosuquidar with daunorubicin and cytarabine in acute myeloid leukemia. Leuk Res 2009; 33(8): 1055-61.
84. Robert J. Multidrug resistance in oncology: diagnostic and therapeutic approaches. Eur J Clin Invest 1999; 29(6): 536-45.
85. Teodoridis JM, Strathdee G, Brown R. Epigenetic silencing mediated by CpG island methylation: potential as a therapeutic target and as a biomarker. Drug Resist Updat 2004; 7(4-5): 267-78.
86. Wishart GC, Plumb JA, Going JJ, et al. P-glycoprotein expression in primary breast cancer detected by immunocytochemistry with two monoclonal antibodies. Br J Cancer 1990; 62(5): 758-61.
87. Marie JP, Huet S, Faussat AM, et al. Multicentric evaluation of the MDR phenotype in leukemia. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique Hopitaux de Paris. Leukemia 1997; 11(7): 1086-94.
88. Chevillard S, Vielh P, Validire P, et al. French multicentric evaluation of mdr1 gene expression by RT-PCR in leukemia and solid tumours. Standardization of RT-PCR and preliminary comparisons between RT-PCR and immunohistochemistry in solid tumours. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hopitaux de Paris. Leukemia 1997; 11(7): 1095-106.
89. Trock BJ, Leonessa F, Clarke R. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst 1997; 89(13): 917-31.
90. Takai D, Jones PA. The CpG island searcher: a new WWW resource. In Silico Biol 2003; 3(3): 235-40.
91. Reed K, Hembruff SL, Laberge ML, et al. Hypermethylation of the ABCB1 downstream gene promoter accompanies ABCB1 gene amplification and increased expression in docetaxel-resistant MCF 7 breast tumor cells. Epigenetics 2008; 3(5): 270-80.
92. Chen KG, Wang YC, Schaner ME, et al. Genetic and epigenetic modeling of the origins of multidrug-resistant cells in a human sarcoma cell line. Cancer Res 2005; 65(20): 9388-97.
93. Chin JE, Soffir R, Noonan KE, et al. Structure and expression of the human MDR (P-glycoprotein) gene family. Mol Cell Biol 1989; 9(9): 3808-20.
94. Baker EK, El-Osta A. Epigenetic regulation of multidrug resistance 1 gene expression: profiling CpG methylation status using bisulphite sequencing. Methods Mol Biol 2010; 596: 183-98.
95. Ueda K, Clark DP, Chen CJ, et al. The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation. J Biol Chem 1987; 262(2): 505-8.
96. Kantharidis P, El-Osta A, deSilva M, et al. Altered methylation of the human MDR1 promoter is associated with acquired multidrug resistance. Clin Cancer Res 1997; 3(11): 2025-32.
97. Baker EK, Johnstone RW, Zalcberg JR, et al. Epigenetic changes to the MDR1 locus in response to chemotherapeutic drugs. Oncogene 2005; 24(54): 8061-75.
98. El-Osta A, Kantharidis P, Zalcberg JR, et al. Precipitous release of methyl-CpG binding protein 2 and histone deacetylase 1 from the methylated human multidrug resistance gene (MDR1) on activation. Mol Cell Biol 2002; 22(6): 1844-57.
99. Desiderato L, Davey MW, Piper AA. Demethylation of the human MDR1 5' region accompanies activation of P-glycoprotein expression in a HL60 multidrug resistant subline. Somat Cell Mol Genet 1997; 23(6): 391-400.
100. Kusaba H, Nakayama M, Harada T, et al. Association of 5' CpG demethylation and altered chromatin structure in the promoter region with transcriptional activation of the multidrug resistance 1 gene in human cancer cells. Eur J Biochem 1999; 262(3): 924-32.
101. David GL, Yegnasubramanian S, Kumar A, et al. MDR1 promoter hypermethylation in MCF-7 human breast cancer cells: changes in chromatin structure induced by treatment with 5-Aza-cytidine. Cancer Biol Ther 2004; 3(6): 540-8.
102. Chekhun VF, Kulik GI, Yurchenko OV, et al. Role of DNA hypomethylation in the development of the resistance to doxorubicin in human MCF-7 breast adenocarcinoma cells. Cancer Lett 2006; 231(1): 87-93.
103. Reed K, Hembruff SL, Sprowl JA, et al. The temporal relationship between ABCB1 promoter hypomethylation, ABCB1 expression and acquisition of drug resistance. Pharmacogenomics J 2010: [Epub ahead of print].
104. Reed K, Poulin ML, Yan L, et al. Comparison of bisulfite sequencing PCR with pyrosequencing for measuring differences in DNA methylation. Anal Biochem 2010; 397(1): 96-106.
105. Fryxell KB, McGee SB, Simoneaux DK, et al. Methylation analysis of the human multidrug resistance 1 gene in normal and leukemic hematopoietic cells. Leukemia 1999; 13(6): 910-7.
106. Yatouji S, El-Khoury V, Trentesaux C, et al. Differential modulation of nuclear texture, histone acetylation, and MDR1 gene expression in human drug-sensitive and -resistant OV1 cell lines. Int J Oncol 2007; 30(4): 1003-9.
107. Cameron EE, Bachman KE, Myohanen S, et al. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet 1999; 21(1): 103-7.
108. Jin S, Scotto KW. Transcriptional regulation of the MDR1 gene by histone acetyltransferase and deacetylase is mediated by NF-Y. Mol Cell Biol 1998; 18(7): 4377-84.
109. Enokida H, Shiina H, Igawa M, et al. CpG hypermethylation of MDR1 gene contributes to the pathogenesis and progression of human prostate cancer. Cancer Res 2004; 64(17): 5956-62.
110. Lin Q, Geng J, Ma K, et al. RASSF1A, APC, ESR1, ABCB1 and HOXC9, but not p16INK4A, DAPK1, PTEN and MT1G genes were frequently methylated in the stage I non-small cell lung cancer in China. J Cancer Res Clin Oncol 2009; 135(12): 1675-84.
111. Muggerud AA, Ronneberg JA, Warnberg F, et al. Frequent aberrant DNA methylation of ABCB1, FOXC1, PPP2R2B and PTEN in ductal carcinoma in situ and early invasive breast cancer. Breast Cancer Res 2010; 12(1): R3.
112. Tahara T, Arisawa T, Shibata T, et al. Effect of promoter methylation of multidrug resistance 1 (MDR1) gene in gastric carcinogenesis. Anticancer Res 2009; 29(1): 337-41.
113. Odenike OM, Alkan S, Sher D, et al. Histone deacetylase inhibitor romidepsin has differential activity in core binding factor acute myeloid leukemia. Clin Cancer Res 2008; 14(21): 7095-101.
114. Ballestar E, Esteller M. The impact of chromatin in human cancer: linking DNA methylation to gene silencing. Carcinogenesis 2002; 23(7): 1103-9.
115. Bhattacharyya NP, Skandalis A, Ganesh A, et al. Mutator phenotypes in human colorectal carcinoma cell lines. Proc Natl Acad Sci USA 1994; 91(14): 6319-23.
116. Issa JP. DNA methylation as a therapeutic target in cancer. Clin Cancer Res 2007; 13(6): 1634-7.
117. Sigalotti L, Fratta E, Coral S, et al. Epigenetic drugs as pleiotropic agents in cancer treatment: biomolecular aspects and clinical applications. J Cell Physiol 2007; 212(2): 330-44.
118. Palii SS, Van Emburgh BO, Sankpal UT, et al. DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol 2008; 28(2): 752-71.
119. Tuma RS. Epigenetic therapies move into new territory, but how exactly do they work? J Natl Cancer Inst 2009; 101(19): 1300-1.
120. Abele R, Clavel M, Dodion P, et al. The EORTC Early Clinical Trials Cooperative Group experience with 5-aza-2'-deoxycytidine (NSC 127716) in patients with colo-rectal, head and neck, renal carcinomas and malignant melanomas. Eur J Cancer Clin Oncol 1987; 23(12): 1921-4.
121. Issa JP, Garcia-Manero G, Giles FJ, et al. Phase 1 study of lowdose prolonged exposure schedules of the hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in hematopoietic malignancies. Blood 2004; 103(5): 1635-40.
122. Issa JP, Kantarjian HM, Kirkpatrick P. Azacitidine. Nat Rev Drug Discov 2005; 4(4): 275-6.
123. Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006; 106(8): 1794-803.
124. Blum KA, Advani A, Fernandez L, et al. Phase II study of the histone deacetylase inhibitor MGCD0103 in patients with previously treated chronic lymphocytic leukaemia. Br J Haematol 2009; 147(4): 507-14.
125. Munster P, Marchion D, Bicaku E, et al. Clinical and biological effects of valproic acid as a histone deacetylase inhibitor on tumor and surrogate tissues: phase I/II trial of valproic acid and epirubicin/ FEC. Clin Cancer Res 2009; 15(7): 2488-96.
126. Gore SD, Baylin S, Sugar E, et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res 2006; 66(12): 6361-9.
127. Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B, et al. Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia. Blood 2006; 108(10): 3271-9.
128. Plumb JA, Strathdee G, Sludden J, et al. Reversal of drug resistance in human tumor xenografts by 2'-deoxy-5-azacytidineinduced demethylation of the hMLH1 gene promoter. Cancer Res 2000; 60(21): 6039-44.
129. Frost P, Abbruzzese JL, Hunt B, et al. Synergistic cytotoxicity using 2'-deoxy-5-azacytidine and cisplatin or 4-hydroperoxycyclophosphamide with human tumor cells. Cancer Res 1990; 50(15): 4572-7.
130. Lenzi R, Frost P, Abbruzzese JL. Modulation of cisplatin resistance by 2'-deoxy-5-azacytidine in human ovarian tumor cell lines. Anticancer Res 1994; 14(1A): 247-51.
131. Sanchez-Gonzalez B, Yang H, Bueso-Ramos C, et al. Antileukemia activity of the combination of an anthracycline with a histone deacetylase inhibitor. Blood 2006; 108(4): 1174-82.
132. Arce C, Perez-Plasencia C, Gonzalez-Fierro A, et al. A proof-ofprinciple study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer. PLoS One 2006; 1: e98.
133. Ando T, Nishimura M, Oka Y. Decitabine (5-Aza-2' deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells. Leukemia 2000; 14(11): 1915-20.
134. Detich N, Hamm S, Just G, et al. The methyl donor SAdenosylmethionine inhibits active demethylation of DNA: a candidate novel mechanism for the pharmacological effects of SAdenosylmethionine. J Biol Chem 2003; 278(23): 20812-20.
135. Luzhna L, Kovalchuk O. Modulation of DNA methylation levels sensitizes doxorubicin-resistant breast adenocarcinoma cells to radiation-induced apoptosis. Biochem Biophys Res Commun 2010; 392(2): 113-7.
136. Palmisano WA, Divine KK, Saccomanno G, et al. Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res 2000; 60(21): 5954-8.
137. Shames DS, Minna JD, Gazdar AF. Methods for detecting DNA methylation in tumors: from bench to bedside. Cancer Lett 2007; 251(2): 187-98.
138. Ou JN, Torrisani J, Unterberger A, et al. Histone deacetylase inhibitor Trichostatin A induces global and gene-specific DNA demethylation in human cancer cell lines. Biochem Pharmacol 2007; 73(9): 1297-307.
139. Sharma G, Mirza S, Parshad R, et al. CpG hypomethylation of MDR1 gene in tumor and serum of invasive ductal breast carcinoma patients. Clin Biochem 2010; 43(4-5): 373-9.