Reduced expression of the E-cadherin gene and its aberrant DNA methylation in hamster pancreatic tumors

被引:15
|
作者
Shimizu, K
Hanaoka, M
Kato, A
Fujii, H
Honoki, K
Tsujiuchi, T
机构
[1] Kinki Univ, Fac Sci & Engn, Dept Life Sci, Lab Canc Biol & Bioinformat, Higashiosaka, Osaka 5778502, Japan
[2] Nara Med Univ, Dept Orthoped Surg, Kashihara, Nara 6348521, Japan
关键词
pancreatic duct adenocarcinoma; DNA methylation; E-cadherin; hamster; nitrosamine;
D O I
10.1016/j.bbrc.2005.08.037
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
The expression of the E-cadherin gene and its DNA methylation status in the 5' upstream region were investigated in pancreatic duct adenocarcinomas (PDAs) induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters. Female Syrian golden hamsters received 70 mg/kg BOP, followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine then L-methionine and a further administration of 20 mg/kg BOP. A total of 15 PDAs were obtained, along with total RNA for assessment of expression by real-time quantitative reverse transcription-polymerase chain reaction. The expression of the E-cadherin was significantly reduced in PDAs (p < 0.05) compared with normal pancreatic tissue. For the analysis of methylation status, bisulfite sequencing was performed with two normal pancreatic tissues and six tumors. The normal pancreatic tissue was all demethylated in this region of E-cadherin. In contrast, six PDAs were highly methylated, correlating with reduced expression of the E-cadherin. These results suggest that aberrant DNA methylation of the E-cadherin gene may play a role in the development of PDAs induced by BOP in hamsters. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:49 / 53
页数:5
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