Lack of death receptor 4 (<Emphasis Type="Italic">DR4</Emphasis>) expression through gene promoter methylation in gastric carcinoma |
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Authors: | Kyung Hwa Lee Sang Woo Lim Ho Gun Kim Dong Yi Kim Seong Yeob Ryu Jae Kyun Joo Jung Chul Kim Jae Hyuk Lee |
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Institution: | (1) Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, 8 Hakdong, Dongku, Gwangju, 501-757, South Korea;(2) Department of Pathology, Chonnam National University Medical School, 8 Hakdong, Dongku, Gwangju, 501-757, South Korea |
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Abstract: | Background and aims To determine the underlying mechanism for the differential expression, the extent of promoter methylation in tumor necrosis
factor-related apoptosis-inducing ligand (TRAIL)-related genes acting downstream of TRAIL was examined in early and advanced
gastric carcinomas.
Methods The extent of promoter methylation in the DR4, DR5, DcR1, DcR2, and CASP8 genes was quantified using bisulfite modification and methylation-specific polymerase chain reaction.
Results The promoters for DcR1, DcR2, and CASP8 were largely unmethylated in early gastric carcinoma, advanced gastric carcinoma, and controls, with no significant difference
among them. Protein levels of DR4, DcR1, and DcR2 as revealed by immunohistochemistry correlated with the extent of the respective promoter methylation (P < 0.05 in all cases). Hypomethylation, rather than hypermethylation, of the DR4 promoter was noted in invasive gastric malignancies, with statistical significance (P = 0.003).
Conclusion The promoter methylation status of TRAIL receptors in gastric carcinoma may have clinical implications for improving therapeutic
strategies in patients with gastric carcinoma. |
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Keywords: | Methylation DR4 Gastric carcinoma TRAIL |
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