Suppression of DPYD expression in RKO Cells via DNA methylation in the regulatory region of the DPYD promoter: A potentially important epigenetic mechanism regulating DPYD expression

Biochemistry and Cell Biology

Volumn 85, Issue 3, 2007, Pages 337-346

  Zhang, Xue ^a   Soong, Richie ^b   Wang, Kangsheng ^c   Li, Lin ^d   Davie, James R ^d   Guarcello, Vincenzo ^c   Diasio, Robert B ^a  

^a MAYO CLINIC CANCER CENTER   (United States)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^c UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^d UNIVERSITY OF MANITOBA   (Canada)

Author keywords

Colorectal cancer RKO cell line; Dihydropyrimidine dehydrogenase; DNA methylation; DPYD; Promoter

Indexed keywords

CELLS; DNA; METHYLATION; ONCOLOGY; TOXICITY;

COLORECTAL CANCER RKO CELL LINE; DIHYDROPYRIMIDINE DEHYDROGENASE; DNA METHYLATION; FLUOROURACIL;

GENE EXPRESSION;

5 AZA 2' DEOXYCYTIDINE; DIHYDROPYRIMIDINE DEHYDROGENASE; FLUOROURACIL; HISTONE DEACETYLASE; TRANSCRIPTION FACTOR SP1; TRICHOSTATIN A;

ARTICLE; CANCER RESEARCH; CHROMATIN IMMUNOPRECIPITATION; COLORECTAL CANCER; CONTROLLED STUDY; DNA METHYLATION; DOWN REGULATION; DPYD GENE; DRUG SENSITIVITY; GENE; GENE EXPRESSION; GENE INACTIVATION; HUMAN; HUMAN CELL; PROTEIN BINDING; PROTEIN EXPRESSION; TRANSCRIPTION REGULATION;

AZACITIDINE; BASE SEQUENCE; CELL LINE, TUMOR; COLORECTAL NEOPLASMS; DIHYDROURACIL DEHYDROGENASE (NADP); DNA METHYLATION; DNA PRIMERS; DNA, NEOPLASM; EPIGENESIS, GENETIC; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HUMANS; HYDROXAMIC ACIDS; PROMOTER REGIONS (GENETICS); RNA, MESSENGER; RNA, NEOPLASM; SP1 TRANSCRIPTION FACTOR; SUPPRESSION, GENETIC;

EID: 33947587702     PISSN: 08298211     EISSN: None     Source Type: Journal    
DOI: 10.1139/O07-009     Document Type: Article

References (37)

1. Anan, K., Mitsuyama, S., Tamae, K., Suehara, N., Nishihara, K., Ogawa, Y., et al. 2003. Increased dihydropyrimidine dehydrogenase activity in breast cancer. J. Surg. Oncol. 82: 174-179.
2. Blanquicett, C., Johnson, M.R., Heslin, M., and Diasio, R.B. 2002. Housekeeping gene variability in normal and carcinomatous colorectal and liver tissues: applications in pharmacogenomic gene expression studies. Anal. Biochem. 303: 209-214.
3. Cameron, E.E., Bachman, K.E., Myohanen, S., Herman, J.G., and Baylin, S.B. 1999. Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat. Genet. 21: 103-107.
4. Chan, Y., Fish, J.E., D'Abreo, C., Lin, S., Robb, G.B., Teichert, A.M., et al. 2004. The cell-specific expression of endothelial nitric-oxide synthase: a role for DNA methylation. J. Biol. Chem. 279: 35087-35100.
5. Collie-Duguid, E.S., Johnston, S.J., Boyce, L., Smith, N., Cowie-son, A., Cassidy, J., et al. 2001. Thymidine phosphorylase and dihydropyrimidine dehydrogenase protein expression in colorectal cancer. Int. J. Cancer, 94: 297-301.
6. Diasio, R.B., and Johnson, M.R. 1999. Dihydropyrimidine dehydrogenase: its role in 5-fluorouracil clinical toxicity and tumor resistance. Clin. Cancer Res. 5: 2672-2673.
7. Dobritzsch, D., Schneider, G., Schnackerz, K.D., and Lindgvist, Y. 2001. Crystal structure of dihydropyrimidine dehydrogenase, a major determinant of the pharmacokinetics of the anti-cancer drug 5-fluorouracil. EMBO J. 20: 650-660.
8. Ezzeldin, H.H., Lee, A.M., Mattison, L.K., and Diasio, R.B. 2005. Methylation of the DPYD promoter: an alternative mechanism for dihydropyrimidine dehydrogenase deficiency in cancer patients. Clin. Cancer Res. 11: 8699-8705.
9. Fujiwaki, R., Hata, K., Nakayama, K., Fukumoto, M., and Miyazaki, K. 2000. Gene expression for dihydropyrimidine dehydrogenase and thymidine phosphorylase influences outcome in epithelial ovarian cancer. J. Clin. Oncol. 18: 3946-3951.
10. Fujiwara, H., Terashima, M., Irinoda, T., Takagane, A., Abe, K., Kashiwaba, M., et al. 2002. Quantitative measurement of thymidylate synthase and dihydropyrimidine dehydrogenase mRNA level in gastric cancer by real-time RT-PCR. Jpn. J. Cancer Res. 93: 1342-1350.
11. Fukushima, M., Morita, M., Ikeda, K., and Nagayama, S. 2003. Population study of expression of thymidylate synthase and dihydropyrimidine dehydrogenase in patients with solid tumors. Int. J. Mol. Med. 12: 839-844.
12. Goffin, J., and Eisenhauer, E. 2002. DNA methyltransferase inhibitors-state of the art. Ann. Oncol. 13: 1699-1716. doi:10.1093/annonc/mdf314.
13. He, S., Sun, J.M., Li, L., and Davie, J.R. 2005. Differential intranuclear organization of transcription factors sp1 and sp3. Mol. Biol. Cell, 16: 4073-4083.
14. Herman, J.G., Graff, J.R., Myohanen, S., Nelkin, B.D., and Baylin, S.B. 1996. Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc. Natl. Acad. Sci. U.S.A. 93: 9821-9826.
15. Jain, P.K. 2003. Epigenetics: the role of methylation in the mechanism of action of tumor suppressor genes. Ann. N.Y. Acad. Sci. 983: 71-83.
16. Johnson, M.R., Wang, K., Smith, J.B., Heslin, M.J., and Diasio, R.B. 2000. Quantitation of dihydropyrimidine dehydrogenase expression by real-time reverse transcription polymerase chain reaction. Anal. Biochem. 278: 175-184.
17. Johnston, S.J., Ridge, S.A., Cassidy, J., and McLeod, H.L. 1999. Regulation of dihydropyrimidine dehydrogenase in colorectal cancer. Clin. Cancer Res. 5: 2566-2570.
18. Jubb, A.M., Quirke, P., and Oates, A.J. 2003. DNA methylation, a biomarker for colorectal cancer: implications for screening and pathological utility. Ann. N. Y. Acad. Sci. 983: 251-267.
19. Lu, Q., and Richardson, B. 2004. Methods for analyzing the role of DNA methylation and chromatin structure in regulating T lymphocyte gene expression. Biol. Proced. Online, 6: 189-203.
20. Mattison, L.K., Fourie, J., Hirao, Y., Koga, T., Desmond, R.A., King, J.R., et al. 2006. The uracil breath test in the assessment of dihydropyrimidine dehydrogenase activity: pharmacokinetic relationship between expired 13CO2 and plasma [2-13C]dihydrouracil. Clin. Cancer Res. 12: 549-555.
21. Mattison, L.K., Soong, R., and Diasio, R.B. 2002. Implications of dihydropyrimidine dehydrogenase on 5-fluorouracil pharmacogenetics and pharmacogenomics. Pharmacogenomics, 3: 485-492.
22. McLeod, H.L., Sludden, J., Murray, G.I., Keenan, R.A., Davidson, A.I., Park, K., et al. 1998. Characterization of dihydropyrimidine dehydrogenase in human colorectal tumours. Br. J. Cancer, 77: 461-465.
23. Momparler, R.L. 2003. Cancer epigenetics. Oncogene, 22: 6479-6483. doi:10.1038/sj.onc.1206774.
24. Mulero-Navarro, S., Carvajal-Gonzalez, J.M., Herranz, M., Ballestar, E., Fraga, M.F., Ropero, S., et al. 2006. The dioxin receptor is silenced by promoter hypermethylation in human acute lymphoblastic leukemia through inhibition of Sp1 binding. Carcinogenesis, 27: 1099-1104.
25. Nagakawa, T., Kayahara, M., Ohta, T., Kitagawa, H., Mikami, K., Kurate, T., and Otsugi, S. 2000. Dihydropyrimidine dehydrogenase activity in human pancreatic tumor tissues. Cancer Invest. 18: 516-520.
26. Naguib, F.N., el Kouni, M.H., and Cha, S. 1985. Enzymes of uracil catabolism in normal and neoplastic human tissues. Cancer Res. 45: 5405-5412.
27. Ohtani-Fujita, N., Fujita, T., Aoike, A., Osifchin, N.E., Robbins, P.D., and Sakai, T. 1993. CpG methylation inactivates the promoter activity of the human retinoblastoma tumor-suppressor gene. Oncogene, 8: 1063-1067.
28. Patel, A., Groopman, J.D., and Umar, A. 2003. DNA methylation as a cancer-specific biomarker: from molecules to populations. Ann. N. Y. Acad. Sci. 983: 286-297.
29. Shestopal, S.A., Johnson, M.R., and Diasio, R.B. 2000. Molecular cloning and characterization of the human dihydropyrimidine dehydrogenase promoter. Biochim. Biophys. Acta, 1494: 162-169.
30. Shin, T.H., Paterson, A.J., Grant, J.H., III, Meluch, A.A., and Kudlow, J.E. 1992. 5-Azacytidine treatment of HA-A melanoma cells induces Spl activity and concomitant transforming growth factor alpha expression. Mol. Cell. Biol. 12: 3998-4006.
31. Takabayashi, A., Iwata, S., Kawai, Y., Kanai, M., Taki, Y., Takechi, T., and Fukushima, M. 2000. Dihydropyrimidine dehydrogenase activity and mRNA expression in advanced gastric cancer analyzed in relation to effectiveness of preoperative 5-fluorouracil-based chemotherapy. Int. J. Oncol. 17: 889-895.
32. Ueda, M., Kitaura, K., Kusada, O., Mochizuki, Y., Yamada, N., Terai, Y., et al. 2000. Regulation of dihydropyrimidine dehydrogenase and pyrimidine nucleoside phosphorylase activities by growth factors and subsequent effects on 5-fluorouracil sensitivity in tumor cells. Jpn. J. Cancer Res. 91: 1185-1191.
33. Ukon, K., Tanimoto, K., Shimokuni, T., Noguchi, T., Hiyama, K., Tsujimoto, H., et al. 2005. Activator protein accelerates dihydropyrimidine dehydrogenase gene transcription in cancer cells. Cancer Res. 65: 1055-1062.
34. Van Kuilenburg, A.B., Vreken, P., Abeling, N.G., Bakker, H.D., Meinsma, R., Van Lenthe, H., et al. 1999. Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Hum. Genet. 104: 1-9.
35. Wang, G., Wei, L.N., and Loh, H.H. 2003. Transcriptional regulation of mouse delta-opioid receptor gene by CpG methylation: involvement of Sp3 and a methyl-CpG-binding protein, MBD2, in transcriptional repression of mouse delta-opioid receptor gene in Neuro2A cells. J. Biol. Chem. 278: 40550-40556.
36. Zhang, X., Li, L., Fourie, J., Davie, J.R., Guarcello, V., and Diasio, R.B. 2006. The role of Sp1 and Sp3 in the constitutive DPYD gene expression. Biochim. Biophys. Acta, 1759: 247-256.
37. Zhu, W.G., Srinivasan, K., Dai, Z., Duan, W., Druhan, L.J., Ding, H., et al. 2003. Methylation of adjacent CpG sites affects Sp1/Sp3 binding and activity in the p21(Cip1) promoter. Mol. Cell. Biol. 23: 4056-4065.