Genomics & Informatics

Korea Genome Organization (한국유전체학회)
권호 표지
DOI QR코드

DOI QR Code

Recovery of Genes Epigenetically Altered by the Histone Deacetylase Inhibitor Scriptaid and Demethylating Agent 5-Azacytidine in Human Leukemia Cells

  • Park, Eun-Kyung (Diagnostic DNA Chip Center, Seoul National University College of Medicine) ;
  • Jeon, Eun-Hyung (Diagnostic DNA Chip Center, Seoul National University College of Medicine) ;
  • Kim, In-Ho (Diagnostic DNA Chip Center, Seoul National University College of Medicine) ;
  • Park, Seon-Yang (Diagnostic DNA Chip Center, Seoul National University College of Medicine)
  • Accepted : 2010.12.02
  • Published : 2010.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Histone deacetylation and demethylation are epigenetic mechanisms implicated in cancer. Studies regarding the role of modulation of gene expression utilizing the histone deacetylase inhibitor scriptaid and the demethylating agent 5-azacytidine in HL-60 leukemia cells have been limited. We studied the possibility of recovering epigenetically silenced genes by scriptaid and 5-azacytidine in human leukemia cells by DNA microarray analysis. The first group was leukemia cells that were cultured with 5-azacytidine. The second group was cultured with scriptaid. The other group was cultured with both agents. Two hundred seventy newly developed genes were expressed after the combination of 5-azacytidine and scriptaid. Twenty-nine genes were unchanged after the combination treatment of 5-azacytidine and scriptaid. Among the 270 genes, 13 genes were differed significantly from the control. HPGD, CPA3, CEACAM6, LOC653907, ETS1, RAB37, PMP22, FST, FOXC1, and CCL2 were up-regulated, and IGLL3, IGLL1, and ASS1 were down-regulated. Eleven genes associated with oncogenesis were found among the differentially expressed genes: ETS1, ASCL2, BTG2, BTG1, SLAMF6, CDKN2D, RRAS, RET, GIPC1, MAGEB, and RGL4. We report the results of our leukemia cell microarray profiles after epigenetic combination therapy with the hope that they are the starting point of selectively targeted epigenetic therapy.

Keywords

References

  1. Bali, P., Pranpat, M., Bradner, J., Balasis, M., Fiskus, W., Guo, F., Rocha, K., Kumaraswamy, S., Boyapalle, S., and Atadja, P. (2005). Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90. J. Biol. Chem. 280, 26729. https://doi.org/10.1074/jbc.C500186200
  2. Benabdallah, B., Bouchentouf, M., Rousseau, J., and Tremblay, J. (2009). Overexpression of follistatin in human myoblasts increases their proliferation and differentiation, and improves the graft success in SCID mice. Cell Transplantation 18, 709-718. https://doi.org/10.3727/096368909X470865
  3. Bishton, M., Kenealy, M., Johnstone, R., Rasheed, W., and Prince, H. (2007). Epigenetic targets in hematological malignancies: combination therapies with HDACis and demethylating agents. Expert Review of Anticancer Therapy 7, 1439-1449. https://doi.org/10.1586/14737140.7.10.1439
  4. Bossers, K., Wirz, K., Meerhoff, G., Essing, A., van Dongen, J., Houba, P., Kruse, C., Verhaagen, J., and Swaab, D. (2010). Concerted changes in transcripts in the prefrontal cortex precede neuropathology in Alzheimer's disease. Brain 133, 3699-3723. https://doi.org/10.1093/brain/awq258
  5. Cameron, E., Bachman, K., Myohanen, S., Herman, J., and Baylin, S. (1999). Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nature Genet. 21, 103-107. https://doi.org/10.1038/5047
  6. Cannons, J., Qi, H., Lu, K., Dutta, M., Gomez-Rodriguez, J., Cheng, J., Wakeland, E., Germain, R., and Schwartzberg, P. (2010). Optimal germinal center responses require a multistage T cell: B cell adhesion process involving integrins, SLAM-associated protein, and CD84. Immunity 32, 253-265. https://doi.org/10.1016/j.immuni.2010.01.010
  7. Chavez-Blanco, A., Perez-Plasencia, C., Perez-Cardenas, E., Carrasco-Legleu, C., Rangel-Lopez, E., Segura-Pacheco, B., Taja-Chayeb, L., Trejo-Becerril, C., Gonzalez-Fierro, A., and Candelaria, M. (2006). Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines. Cancer Cell Int. 6, 2. https://doi.org/10.1186/1475-2867-6-2
  8. Dalgard, C., Van Quill, K., and O'Brien, J. (2008). Evaluation of the in vitro and in vivo antitumor activity of histone deacetylase inhibitors for the therapy of retinoblastoma. Clin. Cancer Res. 14, 3113. https://doi.org/10.1158/1078-0432.CCR-07-4836
  9. Desmond, J., Raynaud, S., Tung, E., Hofmann, W., Haferlach, T., and Koeffler, H. (2007). Discovery of epigenetically silenced genes in acute myeloid leukemias. Leukemia 21, 1026-1034.
  10. Dobashi, S., Katagiri, T., Hirota, E., Ashida, S., Daigo, Y., Shuin, T., Fujioka, T., Miki, T., and Nakamura, Y. (2009). Involvement of TMEM22 overexpression in the growth of renal cell carcinoma cells. Oncol. Reports 21, 305.
  11. Farioli-Vecchioli, S., Tanori, M., Micheli, L., Mancuso, M., Leonardi, L., Saran, A., Ciotti, M., Ferretti, E., Gulino, A., and Pazzaglia, S. (2007). Inhibition of medulloblastoma tumorigenesis by the antiproliferative and pro-differentiative gene PC3. The FASEB J. 21, 2215. https://doi.org/10.1096/fj.06-7548com
  12. Feyerabend, T., Hausser, H., Tietz, A., Blum, C., Hellman, L., Straus, A., Takahashi, H., Morgan, E., Dvorak, A., and Fehling, H. (2005). Loss of histochemical identity in mast cells lacking carboxypeptidase A. Mol. Cell. Biol. 25, 6199. https://doi.org/10.1128/MCB.25.14.6199-6210.2005
  13. Galm, O., Herman, J., and Baylin, S. (2006). The fundamental role of epigenetics in hematopoietic malignancies. Blood Rev. 20, 1-13. https://doi.org/10.1016/j.blre.2005.01.006
  14. Han, S., Kwak, T., Her, K., Cho, Y., Choi, C., Lee, H., Hong, S., Park, Y., Kim, Y., and Kim, T. (2007). CEACAM5 and CEACAM6 are major target genes for Smad3-mediated TGF-a signaling. Oncogene 27, 675-683.
  15. Huang, Y., Tan, M., Gosink, M., Wang, K., and Sun, Y. (2002). Histone deacetylase 5 is not a p53 target gene, but its overexpression inhibits tumor cell growth and induces apoptosis. Cancer Res. 62, 2913.
  16. Ito, T., Ikeda, K., Tomita, K., and Yokoyama, S. (2010). Interleukin-6 upregulates the expression of PMP22 in cultured rat Schwann cells via a JAK2-dependent pathway. Neuro. Lett. 472, 104-108. https://doi.org/10.1016/j.neulet.2010.01.061
  17. Iwai, K., Hirata, K., Ishida, T., Takeuchi, S., Hirase, T., Rikitake, Y., Kojima, Y., Inoue, N., Kawashima, S., and Yokoyama, M. (2004). An anti-proliferative gene BTG1 regulates angiogenesis in vitro . Biochem. Biophys. Res. Commun. 316, 628-635. https://doi.org/10.1016/j.bbrc.2004.02.095
  18. Jantscheff, P., Terracciano, L., Lowy, A., Glatz-Krieger, K., Grunert, F., Micheel, B., Brummer, J., Laffer, U., Metzger, U., and Herrmann, R. (2003). Expression of CEACAM6 in resectable colorectal cancer: a factor of independent prognostic significance. J. Clin. Oncol. 21, 3638. https://doi.org/10.1200/JCO.2003.55.135
  19. Jubb, A., Chalasani, S., Frantz, G., Smits, R., Grabsch, H., Kavi, V., Maughan, N., Hillan, K., Quirke, P., and Koeppen, H. (2006). Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in intestinal neoplasia. Oncogene 25, 3445-3457. https://doi.org/10.1038/sj.onc.1209382
  20. Kawaguchi, Y., Kovacs, J., McLaurin, A., Vance, J., Ito, A., and Yao, T. (2003). The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115, 727-738. https://doi.org/10.1016/S0092-8674(03)00939-5
  21. Kim, B., Ryu, M., Oh, S., and Lim, I. (2008). TIS21/BTG2 negatively regulates estradiol stimulated expansion of hematopoietic stem cells by derepressing akt phosphorylation and inhibiting mTOR signal transduction. Stem Cells 26, 2339-2348. https://doi.org/10.1634/stemcells.2008-0327
  22. Lasa, A., Serrano, E., Carricondo, M., Carnicer, M., Brunet, S., Badell, I., Sierra, J., Aventin, A., and Nomdedeu, J. (2008). High expression of CEACAM6 and CEACAM8 mRNA in acute lymphoblastic leukemias. Ann. Hematol. 87, 205-211. https://doi.org/10.1007/s00277-007-0388-1
  23. Lim, S., Cho, H., Lee, T., Choi, C., Min, Y., Kim, S., and Kim, K. (2010). Impacts of Cytosolic Phospholipase A2, 15-Prostaglandin Dehydrogenase, and Cyclooxygenase-2 Expressions on Tumor Progression in Colorectal Cancer. Yonsei Medical J. 51, 692. https://doi.org/10.3349/ymj.2010.51.5.692
  24. Litkouhi, B., Fleming, E., Welch, W., Berkowitz, R., Birrer, M., and Mok, S. (2008). Overexpression of CEACAM6 in borderline and invasive mucinous ovarian neoplasms. Gynecol. Oncol. 109, 234-239. https://doi.org/10.1016/j.ygyno.2008.01.031
  25. Muggerud, A., Ronneberg, J., Warnberg, F., Botling, J., Busato, F., Jovanovic, J., Solvang, H., Bukholm, I., Borresen-Dale, A., and Kristensen, V. (2010). Frequent aberrant DNA methylation of ABCB1, FOXC1, PPP2R2B and PTEN in ductal carcinoma in situ and early invasive breast cancer. Breast Cancer Res. 12, R3. https://doi.org/10.1186/bcr2466
  26. Pham, H., Chen, M., Li, A., King, J., Angst, E., Dawson, D., Park, J., Reber, H., Hines, O., and Eibl, G. (2010). Loss of 15-hydroxyprostaglandin dehydrogenase increases prostaglandin E2 in pancreatic tumors. Pancreas 39, 332. https://doi.org/10.1097/MPA.0b013e3181baecbe
  27. Qian, D., Kachhap, S., Collis, S., Verheul, H., Carducci, M., Atadja, P., and Pili, R. (2006). Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Res. 66, 8814. https://doi.org/10.1158/0008-5472.CAN-05-4598
  28. Rasheed, W., Johnstone, R., and Prince H. (2007). Histone deacetylase inhibitors in cancer therapy. Expert Opin. Investig. Drugs 16, 659-678. https://doi.org/10.1517/13543784.16.5.659
  29. Russell, L., and Garrett-Sinha, L. (2010). Transcription factor Ets-1 in cytokine and chemokine gene regulation. Cytokine 51, 217-226. https://doi.org/10.1016/j.cyto.2010.03.006
  30. Skubitz, K., and Skubitz, A. (2008). Interdependency of CEACAM-1,-3,-6, and-8 induced human neutrophil adhesion to endothelial cells. J. Translational Medicine 6, 78. https://doi.org/10.1186/1479-5876-6-78
  31. Tatsuwaki, H., Tanigawa, T., Watanabe, T., Machida, H., Okazaki, H., Yamagami, H., Shiba, M., Watanabe, K., Tominaga, K., and Fujiwara, Y. (2010). Reduction of 15 hydroxyprostaglandin dehydrogenase expression is an independent predictor of poor survival associated with enhanced cell proliferation in gastric adenocarcinoma. Cancer Sci. 101, 550-558. https://doi.org/10.1111/j.1349-7006.2009.01390.x
  32. Thiel, A., Ganesan, A., Mrena, J., Junnila, S., Nykanen, A., Hemmes, A., Tai, H., Monni, O., Kokkola, A., and Haglund, C. (2009). 15-hydroxyprostaglandin dehydrogenase is down-regulated in gastric cancer. Clin. Cancer Res. 15, 4572. https://doi.org/10.1158/1078-0432.CCR-08-2518
  33. Thill, M., Fischer, D., Kelling, K., Hoellen, F., Dittmer, C., Hornemann, A., Salehin, D., Diedrich, K., Friedrich, M., and Becker, S. (2010). Expression of vitamin D receptor (VDR), cyclooxygenase-2 (COX-2) and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in benign and malignant ovarian tissue and 25-hydroxycholecalciferol (25 (OH2) D3) and prostaglandin E2 (PGE2) serum level in ovarian cancer patients. J. Stero. Biochem. Mol. Biol. 121, 387-390. https://doi.org/10.1016/j.jsbmb.2010.03.049
  34. van der Flier, L., van Gijn, M., Hatzis, P., Kujala, P., Haegebarth, A., Stange, D., Begthel, H., van den Born, M., Guryev, V., and Oving, I. (2009). Transcription factor achaete scute-like 2 controls intestinal stem cell fate. Cell 136, 903-912. https://doi.org/10.1016/j.cell.2009.01.031
  35. Wang, X., Chorley, B.N., Pittman, G.S., Kleeberger, S.R., Brothers, J. 2nd., Liu, G., Spira, A., and Bell, DA. (2010). Genetic variation and antioxidant response gene expression in the bronchial airway epithelium of smokers at risk for lung cancer. PloS One 5, e11934. https://doi.org/10.1371/journal.pone.0011934
  36. Wu, C., Tseng, R., Hsu, H., Wang, Y., and Hsu, M. (2009). Frequent down-regulation of hRAB37 in metastatic tumor by genetic and epigenetic mechanisms in lung cancer. Lung Cancer 63, 360-367. https://doi.org/10.1016/j.lungcan.2008.06.014