| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Cancer Research Institute [S. H. S., H-S. J., H. H. C., Y-J. B.], and Departments of Tumor Biology [S. H. S., H-S. J., Y-J. B.] and Internal Medicine [N. K. K., Y-J. B.], Seoul National University College of Medicine, Seoul 110-799, Korea, and Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan [H. I., T. T.]
It has been well established that overexpression of Cyclooxygenase-2 (Cox-2) in epithelial cells inhibits apoptosis and increases the invasiveness of malignant cells, favoring tumorigenesis and metastasis. However, the molecular mechanism that regulates Cox-2 expression has not been well defined in gastric carcinoma. In this study, we examined whether the Cox-2 expression could be regulated by hyper-methylation of the Cox-2 CpG island (spanning from -590 to +186 with respect to the transcription initiation site) in human gastric carcinoma cell lines. By Southern analysis, we found that three gastric cells (SNU-601, -620, and -719) without Cox-2 expression demonstrated hyper-methylation at the Cox-2 CpG island. A detailed methylation pattern using bisulfite sequencing analysis revealed that all of the CpG sites were completely methylated in SNU-601. Treatment with demethylating agents effectively reactivated the expression of Cox-2 and restored IL-1ß sensitivity in the previously resistant SNU-601. By transient transfection experiments, we demonstrate that constitutively active Cox-2 promoter activities were exhibited even without an exogenous stimulation in SNU-601. Furthermore, when the motif of the nuclear factor for interleukin-6 expression site, the cyclic AMP response element, or both was subjected to point mutation, the constitutive luciferase activity was markedly reduced. In addition, Cox-2 promoter activity was completely blocked by in vitro methylation of all of the CpG sites in the Cox-2 promoter region with SssI (CpG) methylase in SNU-601. Taken together, these results indicate that transcriptional repression of Cox-2 is caused by hyper-methylation of the Cox-2 CpG island in gastric carcinoma cell lines.
This article has been cited by other articles:
|
|
 |
|
  M. F.G. de Maat, C. J.H. van de Velde, N. Umetani, P. de Heer, H. Putter, A. Q. van Hoesel, G. A. Meijer, N. C. van Grieken, P. J.K. Kuppen, A. J. Bilchik, et al. Epigenetic Silencing of Cyclooxygenase-2 Affects Clinical Outcome in Gastric Cancer J. Clin. Oncol., November 1, 2007; 25(31): 4887 - 4894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xue, Z. Lin, Y.-H. Cheng, C.-C. Huang, E. Marsh, P. Yin, M. P Milad, E. Confino, S. Reierstad, J. Innes, et al. Promoter Methylation Regulates Estrogen Receptor 2 in Human Endometrium and Endometriosis Biol Reprod, October 1, 2007; 77(4): 681 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xue, Z. Lin, P. Yin, M. P. Milad, Y.-H. Cheng, E. Confino, S. Reierstad, and S. E. Bulun Transcriptional Activation of Steroidogenic Factor-1 by Hypomethylation of the 5' CpG Island in Endometriosis J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3261 - 3267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Castells, A. Paya, C. Alenda, F. Rodriguez-Moranta, R. Agrelo, M. Andreu, V. Pinol, S. Castellvi-Bel, R. Jover, X. Llor, et al. Cyclooxygenase 2 expression in colorectal cancer with DNA mismatch repair deficiency. Clin. Cancer Res., March 15, 2006; 12(6): 1686 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Mitchell Unique Suppression of Prostaglandin H Synthase-2 Expression by Inhibition of Histone Deacetylation, Specifically in Human Amnion but Not Adjacent Choriodecidua Mol. Biol. Cell, January 1, 2006; 17(1): 549 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. W. Yim, H.-S. Jong, T. Y. Kim, H. H. Choi, S. G. Kim, S. H. Song, J. Kim, S.-G. Ko, J. W. Lee, T.-Y. Kim, et al. Cyclooxygenase-2 Inhibits Novel Ginseng Metabolite-Mediated Apoptosis Cancer Res., March 1, 2005; 65(5): 1952 - 1960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Soo, T. Putti, Q. Tao, B.-C. Goh, K.-H. Lee, L. Kwok-Seng, L. Tan, and W.-S. Hsieh Overexpression of Cyclooxygenase-2 in Nasopharyngeal Carcinoma and Association With Epidermal Growth Factor Receptor Expression Arch Otolaryngol Head Neck Surg, February 1, 2005; 131(2): 147 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Chang, M. S. Wu, J. T. Lin, B. S. Sheu, T. Muta, H. Inoue, and C.-C. Chen Induction of Cyclooxygenase-2 Overexpression in Human Gastric Epithelial Cells by Helicobacter pylori Involves TLR2/TLR9 and c-Src-Dependent Nuclear Factor-{kappa}B Activation Mol. Pharmacol., December 1, 2004; 66(6): 1465 - 1477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sato, N. Maehara, and M. Goggins Gene Expression Profiling of Tumor-Stromal Interactions between Pancreatic Cancer Cells and Stromal Fibroblasts Cancer Res., October 1, 2004; 64(19): 6950 - 6956. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Jang, H. J. Kang, J. R. Kim, and C. H. Yang Non-steroidal anti-inflammatory drug activated gene (NAG-1) expression is closely related to death receptor-4 and -5 induction, which may explain sulindac sulfide induced gastric cancer cell apoptosis Carcinogenesis, October 1, 2004; 25(10): 1853 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Muller, L. Ivarsson, H. Schrocksnadel, H. Fiegl, A. Widschwendter, G. Goebel, S. Kilga-Nogler, H. Philadelphy, W. Gutter, C. Marth, et al. DNA Methylation Changes in Sera of Women in Early Pregnancy Are Similar to Those in Advanced Breast Cancer Patients Clin. Chem., June 1, 2004; 50(6): 1065 - 1068. [Full Text] [PDF]
|
|
|
|
|
|
G.-C. Hur, S. J. Cho, C.-H. Kim, M. K. Kim, S. I. Bae, S. Y. Nam, J.-W. Park, W. H. Kim, and B. L. Lee Manganese Superoxide Dismutase Expression Correlates with Chemosensitivity in Human Gastric Cancer Cell Lines Clin. Cancer Res., November 15, 2003; 9(15): 5768 - 5775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yuan, R. Z. Luo, S. Fujii, L. Wang, W. Hu, M. Andreeff, Y. Pan, M. Kadota, M. Oshimura, A. A. Sahin, et al. Aberrant Methylation and Silencing of ARHI, an Imprinted Tumor Suppressor Gene in which the Function Is Lost in Breast Cancers Cancer Res., July 15, 2003; 63(14): 4174 - 4180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Maihofner, M. P. Charalambous, U. Bhambra, T. Lightfoot, G. Geisslinger, N. J. Gooderham, and The Colorectal Cancer Group Expression of cyclooxygenase-2 parallels expression of interleukin-1beta, interleukin-6 and NF-kappaB in human colorectal cancer Carcinogenesis, April 1, 2003; 24(4): 665 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Satoh, T. Nakagawachi, H. Nakadate, Y. Kaneko, Z. Masaki, T. Mukai, and H. Soejima Significant Reduction of WT1 Gene Expression, Possibly Due to Epigenetic Alteration in Wilms' Tumor J. Biochem., March 1, 2003; 133(3): 303 - 308. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
