Aberrant silencing of the endocrine peptide gene tachykinin-1 in gastric cancer

被引：14

作者：

David, Stefan ^{[1
]}

Kan, Takatsugu ^{[1
]}

Cheng, Yulan ^{[1
]}

Agarwal, Rachana ^{[1
]}

Jin, Zhe ^{[1
]}

Mori, Yuriko ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21287 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 378卷 / 03期

关键词：

Gastric cancer; Promoter methylation; Microsatellite instability; MSI-H; Substance P; Tachykinin; Real-time quantitative MSP; HELICOBACTER-PYLORI; SUBSTANCE-P; MICROSATELLITE INSTABILITY; DNA METHYLATION; EXPRESSION; HYPERMETHYLATION; PROGRESSION; ACTIVATION; PHENOTYPE; PROMOTER;

D O I：

10.1016/j.bbrc.2008.11.078

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tachykinin-1 (TAC1) is the precursor protein for neuroendocrine peptides, including substance P, and is centrally involved in gastric secretion, motility, mucosal immunity, and cell proliferation. Here we report aberrant silencing of TAC1 in gastric cancer (GC) by promoter hypermethylation. TAC1 methylation and mRNA expression in 47 primary GCs and 41 noncancerous gastric mucosae (NLs) were analyzed by utilizing real-time quantitative PCR-based assays. TAC1 methylation was more prevalent in GCs than in NLs: 21 (45%) of 47 GCs versus 6 (15%) of 41 NLs (p < 0.01). Microsatellite instability was also associated with TAC1 methylation in GCs. There was no significant association between TAC1 methylation and age, gender, stage, histological differentiation, or the presence of Helicobacter pylori. TAC1 mRNA was markedly downregulated in GCs relative to NLs. 5-Aza-2'-deoxycytidine-induced demethylation of the TAC1 promoter resulted in TAC1 mRNA upregulation. Further studies are indicated to elucidate the functional involvement of TAC1 in gastric carcinogenesis. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：605 / 609

页数：5

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