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


CONCLUSIONS
The promoter methylation status of TRAIL receptors in gastric carcinoma may have clinical implications for improving therapeutic strategies in patients with gastric carcinoma.
Department of Pathology, Chonnam National University Medical School, 8 Hakdong, Dongku, Gwangju, 501-757, South Korea.
Kyung Hwa
KH
Lee
Sang Woo
SW
Lim
Ho Gun
HG
Kim
Dong Yi
DY
Kim
Seong Yeob
SY
Ryu
Jae Kyun
JK
Joo
Jung Chul
JC
Kim
Jae Hyuk
JH
Lee
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000502:physiology; D053181:Caspase 8 / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000502:physiology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053319:Tumor Necrosis Factor Decoy Receptors / Q000378:metabolism
D058851:GPI-Linked Proteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; C105190:TNFRSF10A protein, human; C108661:TNFRSF10C protein, human; C451501:TNFRSF10D protein, human; D053319:Tumor Necrosis Factor Decoy Receptors; C505530:CASP8 protein, human; D053181:Caspase 8