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Promoter hypermethylation of cyclooxygenase-2 in gastric carcinoma.
Int J Oncol. 2003 May; 22(5):1025-31.IJ

Abstract

Overexpression of cyclooxygenase-2 (COX-2) is associated with loss of apoptosis, enhancement of proliferation and tumorigenesis. The role of promoter methylation in the transcriptional silencing of cox-2 gene in human gastric cancer is less determined. We investigated 5 gastric cancer cell lines and 58 primary gastric carcinomas for the presence of promoter hypermethylation in cox-2 gene. Combined methylation-specific polymerase chain reaction analysis and bisulfite sequencing analysis revealed that the cox-2 promoter was methylated in 2 of the gastric cancer cell lines. Treatment with 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor, induced COX-2 expression in the methylated gastric cancer cell line. Among the 58 primary gastric cancers, hypermethylation was detected in 25 (43.1%) cases. However, none of the normal gastric tissues showed methylation in cox-2. Promoter hypermethylation was associated with loss of protein expression as determined by immunostaining (p=0.005). Our results indicate that hypermethylation of the CpG island in the cox-2 gene is a major mechanism that mediates transcriptional silencing in a subset of gastric cancers. Thus, gastric cancers with methylation in cox-2 may not be good candidates for treatment with specific COX-2 inhibitors.

Authors+Show Affiliations

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

12684668

Citation

Yu, Jun, et al. "Promoter Hypermethylation of Cyclooxygenase-2 in Gastric Carcinoma." International Journal of Oncology, vol. 22, no. 5, 2003, pp. 1025-31.
Yu J, Leung WK, Lee TL, et al. Promoter hypermethylation of cyclooxygenase-2 in gastric carcinoma. Int J Oncol. 2003;22(5):1025-31.
Yu, J., Leung, W. K., Lee, T. L., Tse, P. C., To, K. F., & Sung, J. J. (2003). Promoter hypermethylation of cyclooxygenase-2 in gastric carcinoma. International Journal of Oncology, 22(5), 1025-31.
Yu J, et al. Promoter Hypermethylation of Cyclooxygenase-2 in Gastric Carcinoma. Int J Oncol. 2003;22(5):1025-31. PubMed PMID: 12684668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Promoter hypermethylation of cyclooxygenase-2 in gastric carcinoma. AU - Yu,Jun, AU - Leung,Wai K, AU - Lee,Tin-Lap, AU - Tse,Pete C H, AU - To,Ka Fai, AU - Sung,Joseph J Y, PY - 2003/4/10/pubmed PY - 2003/8/12/medline PY - 2003/4/10/entrez SP - 1025 EP - 31 JF - International journal of oncology JO - Int J Oncol VL - 22 IS - 5 N2 - Overexpression of cyclooxygenase-2 (COX-2) is associated with loss of apoptosis, enhancement of proliferation and tumorigenesis. The role of promoter methylation in the transcriptional silencing of cox-2 gene in human gastric cancer is less determined. We investigated 5 gastric cancer cell lines and 58 primary gastric carcinomas for the presence of promoter hypermethylation in cox-2 gene. Combined methylation-specific polymerase chain reaction analysis and bisulfite sequencing analysis revealed that the cox-2 promoter was methylated in 2 of the gastric cancer cell lines. Treatment with 5-aza-2'-deoxycytidine, a DNA methyltransferase inhibitor, induced COX-2 expression in the methylated gastric cancer cell line. Among the 58 primary gastric cancers, hypermethylation was detected in 25 (43.1%) cases. However, none of the normal gastric tissues showed methylation in cox-2. Promoter hypermethylation was associated with loss of protein expression as determined by immunostaining (p=0.005). Our results indicate that hypermethylation of the CpG island in the cox-2 gene is a major mechanism that mediates transcriptional silencing in a subset of gastric cancers. Thus, gastric cancers with methylation in cox-2 may not be good candidates for treatment with specific COX-2 inhibitors. SN - 1019-6439 UR - https://www.unboundmedicine.com/medline/citation/12684668/Promoter_hypermethylation_of_cyclooxygenase_2_in_gastric_carcinoma_ L2 - https://www.spandidos-publications.com/ijo/22/5/1025 DB - PRIME DP - Unbound Medicine ER -