Liver-specific Ldb1 deletion results in enhanced liver cancer development.
Liver-specific Ldb1 deletion results in enhanced liver cancer development.
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DOI：
10.1016/j.jhep.2010.05.027
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发表时间：
2010-12
影响因子：
25.7
通讯作者：
Galle PR
中科院分区：
文献类型：
--
作者：
Teufel A;Maass T;Strand S;Kanzler S;Galante T;Becker K;Strand D;Biesterfeld S;Westphal H;Galle PR
LIM-domain-binding（Ldb）蛋白不仅在胚胎发育过程中起重要作用，而且在肿瘤发生过程中也起重要作用。我们以前已经证明Ldb 1是高度的生物学和发育相关性，作为一个有针对性的Ldb 1基因在小鼠中的胚胎致死和多效性表型的结果删除。我们现在已经建立了一个肝脏特异性Ldb 1基因敲除，以研究Ldb 1在致癌作用，特别是在肝细胞癌（HCC）的发展，在体内的作用。这些小鼠通过肿瘤大小和数量证明了肝癌的生长显著增强，主张Ldb 1在HCC发展中的重要作用。此外，细胞增殖和抗凋亡能力增强。为了确定由于缺乏Ldb 1的功能障碍，我们进行了15 k小鼠基因微阵列表达分析。我们发现Myc癌基因在微阵列分析中受到调控，并且能够通过证明其下游靶细胞周期蛋白D1的过表达来进一步证实这种调控。此外，我们能够证明肿瘤抑制因子p21的下调。最后，肝脏干细胞标志物EpCAM也被鉴定为在Ldb 1 −/−敲除小鼠中过表达。我们已经确定了Ldb 1在癌症发展中的重要作用。此外，我们提供的证据表明，myc/细胞周期蛋白D1，p21，和EpCAM依赖的信号转导是关键的下游调控这一新的概念，在肝癌的发展。
LIM-domain-binding (Ldb) proteins have been demonstrated to be essential not only to key embryonic developmental processes but also to carcinogenesis. We have previously demonstrated Ldb1 to be of high biological and developmental relevance, as a targeted deletion of the Ldb1 gene in mice results in an embryonic lethal and pleiotropic phenotype. We have now established a liver-specific Ldb1 knock out to investigate the role of Ldb1 in carcinogenesis, in particular in hepatocellular carcinoma (HCC) development, in vivo. These mice demonstrated a significantly enhanced growth of liver cancer by means of tumor size and number, advocating for an essential role of Ldb1 in HCC development. In addition, proliferation and resistance against apoptosis were increased. In order to identify the functional disturbances due to a lack of Ldb1, we performed a 15 k mouse gene microarray expression analysis. We found the Myc oncogene to be regulated in the microarray analysis and were able to further confirm this regulation by demonstrating an over-expression of its downstream target Cyclin D1. Furthermore, we were able to demonstrate a down-regulation of the tumor suppressor p21. Finally, the liver stem cell marker EpCAM was also identified to be over expressed in Ldb1−/− knock out mice. We have established a significant role of Ldb1 in cancer development. Furthermore, we provided evidence for a myc/cyclin D1, p21, and EpCAM-dependent signalling to be key downstream regulators of this novel concept in HCC development.
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影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
DOI：
10.1111/j.1440-1746.2006.04645.x
发表时间：
2007-06-01
影响因子：
4.1
作者：
Hatano, Etsuro
通讯作者：
Hatano, Etsuro
LIM蛋白LMO4和LIM结构域结合蛋白LDB1在口腔鳞状细胞癌中的表达。
影响因子：
8.8
作者：
Mizunuma, H;Miyazawa, J;Sanada, K;Imai, K
通讯作者：
Imai, K
影响因子：
4.8
作者：
Li, W;Liang, XP;Taub, R
通讯作者：
Taub, R
影响因子：
8
作者：
Grutz, G;Forster, A;Rabbitts, TH
通讯作者：
Rabbitts, TH