Differential gene expression profiling of cultured neu-transformed versus spontaneously-transformed rat cholangiocytes and of corresponding cholangiocarcinomas
Differential gene expression profiling of cultured neu-transformed versus spontaneously-transformed rat cholangiocytes and of corresponding cholangiocarcinomas
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DOI：
10.1016/j.yexmp.2010.08.007
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发表时间：
2010-12-01
影响因子：
3.6
通讯作者：
Sirica, Alphonse E.
中科院分区：
文献类型：
--
作者：
Dumur, Catherine I.;Campbell, Deanna J. W.;Sirica, Alphonse E.
在此之前，我们描述了一种原位胆管癌模型，该模型基于将自发转化的低级别恶性大鼠BDE1胆管细胞（BDEsp细胞）与高级别恶性erbB-2/新转化的BDE1胆管细胞（BDEneu细胞）接种到同基因大鼠肝脏的方法，该模型密切模仿了人类癌症早期和晚期的临床特征。我们现在使用基因表达微阵列和定量实时RT-PCR来分析高致瘤性BDEneu细胞和相应肿瘤中与低致瘤性BDEsp细胞和肿瘤中差异表达的基因。与BDEsp细胞、肿瘤和肿瘤源性BDEsp胆管癌细胞相比，在亲本BDEneu细胞、肿瘤和BDEneu肿瘤源性胆管癌细胞中普遍过表达的基因包括Sox17、Krt20、Erbb2和Sphk1。在BDEneu细胞和肿瘤源性胆管癌细胞中，Mud 1也比相应的BDEsp细胞系中表达的Mud 1显著过表达。与BDEsp肿瘤相比，仅由胆管癌相关纤维母细胞产生的Periostin和tenascin-C在BDEneu肿瘤中均显著过表达。有趣的是，与BDEsp细胞相比，amphiregulin是体外BDEneu细胞中显著低表达的基因，但与BDEsp肿瘤相比，在BDEneu肿瘤中显著过表达，并且与BDEneu胆管癌的体内进展相关。我们的数据支持一个独特的动物模型，该模型概括了人类胆管癌进展的重要分子特征，并可能作为一个潜在的强大的临床前平台，用于识别和快速测试胆管癌治疗和/或预防的新型分子靶向策略。(C) 2010爱思唯尔公司版权所有。
Previously, we described an orthotopic cholangiocarcinoma model based on bile duct inoculation of spontaneously-transformed low grade malignant rat BDE1 cholangiocytes (BDEsp cells) compared to high grade malignant erbB-2/neu- transformed BDE1 cholangiocytes (BDEneu cells) into the livers of syngeneic rats, which closely mimics clinical features of early versus advanced stages of the human cancer. We now used gene expression microarray together with quantitative real-time RT-PCR to profile genes differentially expressed in highly tumorigenic BDEneu cells and corresponding tumors compared to less aggressive tumorigenic BDEsp cells and tumors. Genes identified as being commonly overexpressed in parent BDEneu cells, tumors, and in a BDEneu tumor-derived cholangiocarcinoma cell line included Sox17, Krt20, Erbb2, and Sphk1 when respectively compared to BDEsp cells, tumors, and tumor-derived BDEsp cholangiocarcinoma cells. Mud l was also prominently overexpressed in BDEneu cells and tumor-derived cholangiocarcinoma cells over that expressed in corresponding BDEsp cell lines. Periostin and tenascin-C, which were produced exclusively by cholangiocarcinoma-associated fibroblastic cells, were each significantly overexpressed in BDEneu tumors compared to BDEsp tumors. Interestingly, amphiregulin was representative of a gene found to be significantly underexpressed in vitro in BDEneu cells compared to BDEsp cells, but significantly overexpressed in BDEneu tumors compared to BDEsp tumors, and correlated with BDEneu cholangiocarcinoma progression in vivo. Our data support a unique animal model that recapitulates important molecular features of human cholangiocarcinoma progression, and may serve as a potentially powerful preclinical platform for identifying and rapidly testing novel molecular targeting strategies for cholangiocarcinoma therapy and/or prevention. (C) 2010 Elsevier Inc. All rights reserved.