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Lack of death receptor 4 (DR4) expression through gene promoter methylation in gastric carcinoma

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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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Acknowledgments

This study was sponsored by grants from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0720570) and the Brain Korea 21 Project, Center for Biomedical Human Resources at Chonnam National University.

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Authors and Affiliations

  1. Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, 8 Hakdong, Dongku, Gwangju, 501-757, South Korea

    Sang Woo Lim, Ho Gun Kim, Dong Yi Kim, Seong Yeob Ryu, Jae Kyun Joo & Jung Chul Kim

  2. Department of Pathology, Chonnam National University Medical School, 8 Hakdong, Dongku, Gwangju, 501-757, South Korea

    Kyung Hwa Lee & Jae Hyuk Lee

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  1. Kyung Hwa Lee
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Correspondence to Jae Hyuk Lee.

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Lee, K.H., Lim, S.W., Kim, H.G. et al. Lack of death receptor 4 (DR4) expression through gene promoter methylation in gastric carcinoma. Langenbecks Arch Surg 394, 661–670 (2009). https://doi.org/10.1007/s00423-009-0484-x

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  • DOI: https://doi.org/10.1007/s00423-009-0484-x

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