Epigenetic down-regulation and suppressive role of DCBLD2 in gastric cancer cell proliferation and invasion

被引：45

作者：

Kim, Mirang ^{[1
,6
]}

Lee, Kyung-Tae ^{[7
]}

Jang, Hay-Ran ^{[1
]}

Kim, Jeong-Hwan ^{[1
]}

Noh, Seung-Moo ^{[2
]}

Song, Kyu-Sang ^{[3
]}

Cho, June-Sik ^{[4
]}

Jeong, Hyun-Yong ^{[5
]}

Kim, Seon-Young ^{[1
]}

Yoo, Hyang-Sook ^{[1
]}

Kim, Yong Sung ^{[1
,6
]}

机构：

[1] KRIBB, Funct Genom Res Ctr, Taejon 305806, South Korea

[2] Chungnam Natl Univ, Coll Med, Dept Gen Surg, Taejon, South Korea

[3] Chungnam Natl Univ, Coll Med, Dept Pathol, Taejon, South Korea

[4] Chungnam Natl Univ, Coll Med, Dept Diagnost Radiol, Taejon, South Korea

[5] Chungnam Natl Univ, Coll Med, Dept Internal Med, Taejon, South Korea

[6] Univ Sci & Technol, Dept Funct Genom, Taejon, South Korea

[7] Natl Livestock Res Inst, Div Anim Genom & Bioinformat, Suwon, South Korea

来源：

MOLECULAR CANCER RESEARCH | 2008年 / 6卷 / 02期

关键词：

D O I：

10.1158/1541-7786.MCR-07-0142

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-slienced 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.

引用

页码：222 / 230

页数：9

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