This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pompeia, C. Articles by Farrar, W. L. Search for Related Content PubMed PubMed Citation Articles by Pompeia, C. Articles by Farrar, W. L.

Microarray Analysis of Epigenetic Silencing of Gene Expression in the KAS-6/1 Multiple Myeloma Cell Line

¹ Laboratory of Molecular Immunoregulation, and ² Laboratory of Medicinal Chemistry, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland, and ³ Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, Ohio

The epigenetic control of gene transcription in cancer has been the theme of many recent studies and therapeutic approaches. Carcinogenesis is frequently associated with hypermethylation and consequent down-regulation of genes that prevent cancer, e.g., those that control cell proliferation and apoptosis. We used the demethylating drug zebularine to induce changes in DNA methylation, then examined patterns of gene expression using cDNA array analysis and Restriction Landmark Genomic Scanning followed by RNase protection assay and reverse transcription-PCR to confirm the results. Microarray studies revealed that many genes were epigenetically regulated by methylation. We concluded that methylation decreased the expression of, or silenced, several genes, contributing to the growth and survival of multiple myeloma cells. For example, a number of genes (BAD, BAK, BIK, and BAX) involved in apoptosis were found to be suppressed by methylation. Sequenced methylation-regulated DNA fragments identified by Restriction Landmark Genomic Scanning were found to contain CpG islands, and some corresponded to promoters of genes that were regulated by methylation. We also observed that after the removal of the demethylating drug, the addition of interleukin 6 restored CpG methylation and re-established previously silenced gene patterns, thus implicating a novel role of interleukin 6 in processes regulating epigenetic gene repression and carcinogenesis.

This article has been cited by other articles:

				E. De Bruyne, T. J. Bos, K. Asosingh, I. Vande Broek, E. Menu, E. Van Valckenborgh, P. Atadja, V. Coiteux, X. Leleu, K. Thielemans, et al. Epigenetic Silencing of the Tetraspanin CD9 during Disease Progression in Multiple Myeloma Cells and Correlation with Survival Clin. Cancer Res., May 15, 2008; 14(10): 2918 - 2926. [Abstract] [Full Text] [PDF]

				H. Tatetsu, S. Ueno, H. Hata, Y. Yamada, M. Takeya, H. Mitsuya, D. G. Tenen, and Y. Okuno Down-regulation of PU.1 by Methylation of Distal Regulatory Elements and the Promoter Is Required for Myeloma Cell Growth Cancer Res., June 1, 2007; 67(11): 5328 - 5336. [Abstract] [Full Text] [PDF]

				T. Yoshino, H. Shiina, S. Urakami, N. Kikuno, T. Yoneda, K. Shigeno, and M. Igawa Bcl-2 expression as a predictive marker of hormone-refractory prostate cancer treated with taxane-based chemotherapy. Clin. Cancer Res., October 15, 2006; 12(20): 6116 - 6124. [Abstract] [Full Text] [PDF]

				L. Nadav, B.-Z. Katz, S. Baron, N. Cohen, E. Naparstek, and B. Geiger The Generation and Regulation of Functional Diversity of Malignant Plasma Cells. Cancer Res., September 1, 2006; 66(17): 8608 - 8616. [Abstract] [Full Text] [PDF]

				L. Drucker, T. Tohami, S. Tartakover-Matalon, V. Zismanov, H. Shapiro, J. Radnay, and M. Lishner Promoter hypermethylation of tetraspanin members contributes to their silencing in myeloma cell lines Carcinogenesis, February 1, 2006; 27(2): 197 - 204. [Abstract] [Full Text] [PDF]

				C. Balch, P. Yan, T. Craft, S. Young, D. G. Skalnik, T. H-M. Huang, and K. P. Nephew Antimitogenic and chemosensitizing effects of the methylation inhibitor zebularine in ovarian cancer Mol. Cancer Ther., October 1, 2005; 4(10): 1505 - 1514. [Abstract] [Full Text] [PDF]

				D. R. Hodge, W. Xiao, B. Peng, J. C. Cherry, D. J. Munroe, and W. L. Farrar Enforced Expression of Superoxide Dismutase 2/Manganese Superoxide Dismutase Disrupts Autocrine Interleukin-6 Stimulation in Human Multiple Myeloma Cells and Enhances Dexamethasone-Induced Apoptosis Cancer Res., July 15, 2005; 65(14): 6255 - 6263. [Abstract] [Full Text] [PDF]

				Y. Zhang, X.-W. Wang, D. Jelovac, T. Nakanishi, M.-h. Yu, D. Akinmade, O. Goloubeva, D. D. Ross, A. Brodie, and A. W. Hamburger The ErbB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells PNAS, July 12, 2005; 102(28): 9890 - 9895. [Abstract] [Full Text] [PDF]

				D. R. Hodge, B. Peng, J. C. Cherry, E. M. Hurt, S. D. Fox, J. A. Kelley, D. J. Munroe, and W. L. Farrar Interleukin 6 Supports the Maintenance of p53 Tumor Suppressor Gene Promoter Methylation Cancer Res., June 1, 2005; 65(11): 4673 - 4682. [Abstract] [Full Text] [PDF]

				P. W. Laird Cancer epigenetics Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R65 - R76. [Abstract] [Full Text] [PDF]