Reduced expression of the E-cadherin gene and its aberrant DNA methylation in hamster pancreatic tumors
Reduced expression of the E-cadherin gene and its aberrant DNA methylation in hamster pancreatic tumors
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DOI：
10.1016/j.bbrc.2005.08.037
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发表时间：
2005-10-14
影响因子：
3.1
通讯作者：
Tsujiuchi, T
中科院分区：
文献类型：
--
作者：
Shimizu, K;Hanaoka, M;Tsujiuchi, T
本文研究了N-亚硝基双（2-氧代丙基）胺（BOP）诱发的仓鼠胰腺导管腺癌（PDA）中E-钙粘蛋白基因的表达及其5'上游DNA甲基化状态。雌性叙利亚金仓鼠接受70 mg/kg BOP，然后重复暴露于由胆碱缺乏饮食结合DL-乙硫氨酸然后L-甲硫氨酸组成的增强压力方案，并进一步给予20 mg/kg BOP。共获得15个PDA，沿着总RNA用于通过实时定量逆转录-聚合酶链反应评估表达。PDAs中E-cadherin的表达明显低于正常胰腺组织（p < 0.05）。为了分析甲基化状态，对两个正常胰腺组织和六个肿瘤进行亚硫酸氢盐测序。正常胰腺组织中E-cadherin的这一区域全部去甲基化。相比之下，6个PDA高度甲基化，与E-钙粘蛋白表达减少相关。这些结果表明，异常的DNA甲基化的E-钙粘蛋白基因可能发挥作用，在发展中的PDA BOP诱导仓鼠。(c)2005年爱思唯尔公司All rights reserved.
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.