Production of hepatocellular carcinoma by oval cells: cell cycle expression of c-myc and p53 at different stages of oval cell transformation.
Production of hepatocellular carcinoma by oval cells: cell cycle expression of c-myc and p53 at different stages of oval cell transformation.
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发表时间：
1989-03
期刊：
影响因子：
11.2
通讯作者：
Lundy Braun;R. Mikumo;Nelson Fausto
中科院分区：
文献类型：
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作者：
Lundy Braun;R. Mikumo;Nelson Fausto
在维持致癌饮食(胆碱缺乏，含0.1%乙硫氨酸)的大鼠中，c-myc和p53 mRNAs的水平在动物饮食后4wk增加。细胞分离研究表明，c-myc的变化发生在卵圆细胞中，而p53的增加主要发生在卵圆细胞中，但也存在于肝细胞中。为了确定这种增加是细胞增殖的结果还是与转化有关，我们建立了一个体外肝癌发生模型，使用从喂养致癌饮食的大鼠肝脏分离的上皮细胞。该细胞系(LE/6)在传代次数较少的情况下，在体外培养时会发生自发转化。接种S.C.在裸鼠体内转化的细胞中产生了经组织学鉴定为肝细胞癌的肿瘤。我们利用这些细胞系比较了未转化、部分转化和致瘤的LE/6细胞中c-myc和P53mRNAs的细胞周期表达。我们发现，在未转化和部分转化的细胞中，这两个基因的表达都受到细胞周期的控制。然而，该细胞系的完全转化与myc的组成性表达有关，而与p53转录本无关。在这项工作的基础上，我们认为c-myc的结构性表达可能是肝癌发生过程中的晚期事件。
In rats maintained on a carcinogenic diet (choline deficient containing 0.1% ethionine), the levels of c-myc and p53 mRNAs increased by 4 wk after animals were placed on the diet. Cell isolation studies showed that the change in c-myc takes place in oval cells, while p53 increases predominantly in oval cells but also in hepatocytes. To determine whether this increase is a consequence of cell proliferation or is associated with transformation, we have developed an in vitro model of hepatocarcinogenesis using epithelial cells isolated from the livers of rats fed the carcinogenic diet. When maintained in vitro with infrequent subculture, this cell line (LE/6) undergoes spontaneous transformation. Inoculation s.c. of the transformed cells into nude mice yields tumors histologically identified as hepatocellular carcinoma. We have used these cell lines to compare the cell cycle expression of c-myc and p53 mRNAs in untransformed, partially transformed, and tumorigenic LE/6 cells. We find that the expression of both genes is under cell cycle control in untransformed and partially transformed cells. However, complete transformation of this cell line is associated with constitutive expression of myc but not p53 transcripts. On the basis of this work we suggest that constitutive expression of c-myc may be a late event in hepatocarcinogenesis.