E2F1 blocks and c-Myc accelerates hepatic ploidy in transgenic mouse models
E2F1 blocks and c-Myc accelerates hepatic ploidy in transgenic mouse models
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DOI：
10.1016/s0006-291x(03)00125-6
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发表时间：
2003-02-28
影响因子：
3.1
通讯作者：
Thorgeirsson, SS
中科院分区：
文献类型：
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作者：
Conner, EA;Lemmer, ER;Thorgeirsson, SS
以前，我们已经表明，E2 F1或c-Myc的过度表达促进肝癌的发生，E2 F1小鼠获得肝癌比c-Myc转基因小鼠更快。我们还发现E2 F1/c-Myc的共表达进一步加速了肝癌的发展。在这里，我们描述了这两个转录因子的表达失调，也影响肝倍性在出生后的肝脏生长和肿瘤发病前。E2 F1和/或c-Myc的致癌活性与肝细胞增殖的持续增加相关。然而，E2 F1介导的细胞增殖有利于占主导地位的二倍体细胞特征的癌前类型的肝脏生长，而c-Myc的功能，以加速年龄相关的肝细胞多倍化。类似地，E2 F1和c-Myc共表达所赋予的增殖优势增加了年轻时二倍体细胞的频率。因此，E2 F1和c-Myc对肝细胞倍性的相反作用表明，这两种转录因子具有不同的机制，它们通过该机制控制肝脏增殖/成熟并最终控制癌发生。(C)2003 Elsevier Science（美国）。All rights reserved.
Previously, we have shown that over-expression of either E2F1 or c-Myc promotes hepatocarcinogenesis and that E2F1 mice acquire HCC more rapidly than c-Myc transgenic mice. We also found that co-expression of E2F1/c-Myc further accelerates liver cancer development. Here we describe that the deregulated expression of these two transcription factors also affects hepatic ploidy during post-natal liver growth and before the onset of tumors. Oncogenic activity of E2F1 and/or c-Myc was associated with a persistent increase in hepatocyte proliferation. However, E2F1-mediated cell proliferation favored the predominance of diploid cells characteristic of pre-neoplastic type of liver growth whereas c-Myc functioned to accelerate age-related hepatocyte polyploidization. Similarly, proliferative advantage conferred by co-expression of E2F1 and c-Myc increased the frequency of diploid cells at a young age. Thus, the opposing effects of E2F1 and c-Myc on hepatocyte ploidy suggest that these two transcription factors have different mechanisms by which they control liver proliferation/maturation and ultimately, carcinogenesis. (C) 2003 Elsevier Science (USA). All rights reserved.