Expression of the liver-enriched transcription factors C/EBP alpha, C/EBP beta, HNF-1, and HNF-4 in preneoplastic nodules and hepatocellular carcinoma in rat liver.
Expression of the liver-enriched transcription factors C/EBP alpha, C/EBP beta, HNF-1, and HNF-4 in preneoplastic nodules and hepatocellular carcinoma in rat liver.
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DOI：
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发表时间：
1995
影响因子：
4.6
通讯作者：
P. Flodby;D. Liao;A. Blanck;K. Xanthopoulos;I. Hällström
中科院分区：
文献类型：
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作者：
P. Flodby;D. Liao;A. Blanck;K. Xanthopoulos;I. Hällström
采用耐药肝细胞(RH)模型，研究了肝富集转录因子CCAAT/增强子结合蛋白(C/EBP)α、β和肝细胞核因子(HNF)-1、HNF-4在雄性大鼠肝结节和肝细胞癌中的表达。持续性结节中c/EBPα在转录、mRNA和蛋白水平的表达均低于相应周围肝组织。在肿瘤中的表达进一步降低。在RH模型肝部分切除后3wk分离的早期结节中，已经观察到C/EBPα基因转录下调。然而，癌前结节在C/EBPβ、HNF-1和HNF-4的转录或稳态mRNA水平上没有观察到明显的变化。结节中C/EBPβ蛋白略有下降，HNF-1和HNF-4水平下降更为明显，分别为相应周围肝脏水平的67%、37%和46%。总之，在癌前病变和肿瘤性肝脏病变中，观察到了与维持肝细胞分化状态相关的几种转录因子的不同调控。这可能会对肝癌发生过程中一系列基因的调控产生影响。此外，作为负生长调节因子的C/EBPα表达的减弱可能有助于结节在肝癌发生过程中的增殖优势。
The expression patterns of the liver-enriched transcription factors CCAAT/enhancer-binding protein (C/EBP) alpha and beta and hepatocyte nuclear factor (HNF)-1 and HNF-4 were studied in liver nodules and hepatocellular carcinomas from male rats treated according to the resistant hepatocyte (RH) model. C/EBP alpha expression was lower at the transcriptional, mRNA, and protein levels in persistent nodules than in the respective surrounding livers. Expression was further decreased in the tumors. Transcriptional downregulation of C/EBP alpha gene expression was observed already in very early nodules, isolated 3 wk after partial hepatectomy in the RH model. However, no detectable changes were observed in preneoplastic nodules in the transcription or in steady-state mRNA levels of C/EBP beta, HNF-1, and HNF-4. A slight decrease in C/EBP beta protein and a more pronounced attenuation of HNF-1 and HNF-4 levels was observed in nodules, being 67%, 37%, and 46% of the levels in the corresponding surrounding livers, respectively. In conclusion, differential regulation of several transcription factors that are associated with the maintenance of the differentiated state of the hepatocytes was observed in preneoplastic and neoplastic liver lesions. This could have an impact on the regulation of a wide array of genes during liver carcinogenesis. Furthermore, the attenuation of C/EBP alpha expression, regarded as a negative growth regulator, could contribute to the proliferative advantage of nodules during liver carcinogenesis.