Aberrant silencing of the endocrine peptide gene tachykinin-1 in gastric cancer.
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.
David
Stefan
S
Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, 1503 E. Jefferson Street Office #108, Baltimore, MA 21287, USA.
Kan
Takatsugu
T
Cheng
Yulan
Y
Agarwal
Rachana
R
Jin
Zhe
Z
Mori
Yuriko
Y
D000230:Adenocarcinoma / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011498:Protein Precursors / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D015320:Tachykinins / Q000235:genetics*
D011498:Protein Precursors; D015320:Tachykinins; C054618:protachykinin