Identification of differentially expressed genes associated with colorectal cancer liver metastasis
Identification of differentially expressed genes associated with colorectal cancer liver metastasis
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DOI：
10.1159/000070603
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发表时间：
2003-07-01
影响因子：
1.6
通讯作者：
Bustin, SA
中科院分区：
文献类型：
--
作者：
Li, SR;Dorudi, S;Bustin, SA
原发性结直肠肿瘤成功转移至肝脏的分子机制仍不清楚。我们采用抑制性消减杂交（SSH）和反向北方斑点杂交分析，以描绘mRNA表达模式的原发性大肠癌及其肝转移。经SSH和反向北方斑点杂交分析，正向消减文库中有17个克隆和反向消减文库中有13个克隆的差异表达得到证实。四个克隆显示没有显着的序列同一性与任何已知的序列在GenBank数据库中，并可能代表新的基因，其上调或下调与结直肠肝转移。有趣的是，13个下调的克隆中有一个与BRCA 1肿瘤抑制基因显示出99%的序列同一性。由于启动子甲基化是导致约10-20%的人乳腺癌中BRCA 1基因转录沉默的直接原因，我们进一步研究了10个原发性结直肠肿瘤样本的启动子甲基化状态，但未发现启动子甲基化的证据。版权所有（C）2003 S. Karger AG，巴塞尔。
The molecular mechanisms underlying successful metastasis of primary colorectal tumour to the liver remain unknown. We have used suppression subtractive hybridisation (SSH) and reverse Northern dot blot analysis to profile the mRNA expression patterns of a primary colorectal cancer and its liver metastasis. After SSH and reverse Northern dot blot analysis, differential expression was confirmed in 17 clones from the forward, and 13 clones from the reverse subtracted cDNA library. Four clones showed no significant sequence identities with any known sequences in the GenBank data base and likely to represent novel genes whose up- or down-regulation is associated with colorectal liver metastasis. Interestingly, one of the 13 down-regulated clones displayed 99% sequence identity with the BRCA1 tumour suppressor gene. Since promoter methylation is a direct cause of transcription silencing of the BRCA1 gene in approximately 10-20% of human breast cancer we further investigated its promoter methylation status in ten primary colorectal tumour samples, but revealed no evidence of promoter methylation. Copyright (C) 2003 S. Karger AG, Basel.