Proteins related to early changes in carcinogenesis of hepatic oval cells after treatment with methylnitronitrosoguanidine
Proteins related to early changes in carcinogenesis of hepatic oval cells after treatment with methylnitronitrosoguanidine
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甲基亚硝基胍处理后肝卵圆细胞癌变早期变化相关蛋白
DOI：
10.1016/j.etp.2013.11.007
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发表时间：
2014-03-01
影响因子：
--
通讯作者：
Xue, Ling
中科院分区：
文献类型：
--
作者：
Ding, Li;Ding, Yan Na;Xue, Ling
肝卵圆细胞被认为是肝脏的兼性祖细胞/干细胞，并且能够分化为肝细胞或胆管上皮细胞。在动物模型中，经致癌物转化的卵圆细胞具有发生癌变的潜能。为了更好地了解卵巢癌发生过程中的分子机制，我们采用蛋白质组学方法研究了甲基硝基亚硝基胍（MNNG）诱导卵巢卵圆细胞（OC 3 W 3 -15）早期蛋白质表达的变化。同时，通过电镜、流式细胞仪、核型分析和软琼脂染色等方法，比较MNNG处理前后OC 3 W3 -15细胞和对照组卵圆细胞的生物学特性。实时荧光定量PCR检测两种细胞系中GGT和GSTP 1的mRNA水平。我们的研究结果表明，MNNG处理的OC 3 W 3 -15细胞表现出恶性转化的特征，包括生长速度，染色体畸变，异常的DNA含量，并形成集落的能力。与对照细胞相比，细胞表达更高水平的肿瘤标志物AFP、GGT和GSTP 1 mRNA。在OC 3 W3 -15细胞中发现了参与恶性转化过程的几种蛋白质的显著变化，包括细胞周期相关蛋白、参与生物体发育和细胞分化的蛋白质。这些蛋白质可能在肝卵圆细胞恶性转化过程中起早期作用，并有助于进一步了解肝细胞癌的发生机制。(C)2013 Elsevier GmbH. All rights reserved.
Hepatic oval cells are considered as facultative progenitor/stem cells of liver and able to differentiate into either hepatocytes or biliary epithelial cells. The transformed oval cells by carcinogen possess potential to develop carcinomas in animal models. In order to better understand the molecular mechanism in carcinogenetic process, we used a proteomic approach to assess the early changes in protein expression of oval cells (OC3W3-15) initiated by methylnitronitrosoguanidine (MNNG). Meanwhile, we compared cell biologic characteristics of the MNNG treated OC3W3-15 cells and control oval cells by electron microscopy, flow cytometry, karyotype and soft agar assay. The mRNA levels of GGT and GSTP1 determined by real-time PCR were also detected in both cell lines. Our results showed that MNNG-treated OC3W3-15 cells exhibited characteristics of malignant transformation, including growth rate, chromosomal aberrations, abnormal DNA content, and the ability to form colonies. The cells expressed higher levels of the tumor marker AFP, GGT and GSTP1 mRNA than that of control cells. Significant changes of several proteins involved in the malignant transformation process, including cell cycle related proteins, proteins involved in organism development and cell differentiation, are found in OC3W3-15 cells. The proteins may provide early affection in malignant transformation of hepatic oval cells, and yield further insight into mechanism of carcinogenesis of hepatocellular carcinoma. (C) 2013 Elsevier GmbH. All rights reserved.