Epigenetic down-regulation and suppressive role of DCBLD2 in gastric cancer cell proliferation and invasion.
The promoter region of Discoidin, CUB and LCCL domain containing 2 (DCBLD2) was found to be aberrantly methylated in gastric cancer cell lines and in primary gastric cancers, as determined by restriction landmark genomic scanning. DCBLD2 expression was inversely correlated with DCBLD2 methylation in gastric cancer cell lines. Treatment with 5-aza-2'-deoxycytidine and trichostatin A partially reversed DCBLD2 methylation and restored gene expression in DCBLD2-silenced cell lines. In an independent series of 82 paired gastric cancers and adjacent normal tissues, DCBLD2 expression was down-regulated in 79% of gastric cancers as compared with normal tissues as measured by real-time reverse transcription-PCR. Pyrosequencing analysis of the DCBLD2 promoter region revealed abnormal hypermethylation in gastric cancers, and this hypermethylation was significantly correlated with down-regulation of DCBLD2 expression. Furthermore, ectopic expression of DCBLD2 in gastric cancer cell lines inhibited colony formation in both anchorage-dependent and anchorage-independent cultures and also inhibited invasion through the collagen matrix. These data suggest that down-regulation of DCBLD2, often associated with promoter hypermethylation, is a frequent event that may be related to the development of gastric cancer.
Kim
Mirang
M
Functional Genomics Research Center, KRIBB, Yuseong-Gu, Daejeon, Korea.
Lee
Kyung-Tae
KT
Jang
Hay-Ran
HR
Kim
Jeong-Hwan
JH
Noh
Seung-Moo
SM
Song
Kyu-Sang
KS
Cho
June-Sik
JS
Jeong
Hyun-Yong
HY
Kim
Seon-Young
SY
Yoo
Hyang-Sook
HS
Kim
Yong Sung
YS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018899:CpG Islands; D019175:DNA Methylation / Q000187:drug effects; D004262:DNA Restriction Enzymes / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing / Q000187:drug effects; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
C436326:DCBLD2 protein, human; D006877:Hydroxamic Acids; D008565:Membrane Proteins; D012333:RNA, Messenger; C012589:trichostatin A; D004262:DNA Restriction Enzymes; D001374:Azacitidine