Identification of odontogenic ameloblast associated as a novel target gene of the Wnt/β-catenin signaling pathway.
Identification of odontogenic ameloblast associated as a novel target gene of the Wnt/β-catenin signaling pathway.
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Wnt/β-catenin信号通路在发育和癌变中起着关键作用。虽然已经在各种组织和肿瘤中鉴定了该信号传导的一些靶基因，但是对靶基因及其在人类癌症（包括肝癌和结直肠癌）的发展中的作用的全面理解仍有待于充分阐明。在这项研究中，我们使用HuH-7肝癌细胞寻找肝癌中受Wnt信号调节的基因。比较表达活性形式的突变型β-连环蛋白的细胞和表达增强型绿色荧光蛋白（EGFP）的细胞之间的表达谱，鉴定了突变型β-连环蛋白基因（CTNNB 1）上调的7个基因。在这七个基因中，我们重点研究了与牙源性成釉细胞相关的成釉细胞相关的牙源性成釉细胞相关蛋白基因，作为一个新的靶基因。有趣的是，它的表达在肝细胞癌、结直肠腺癌和肝母细胞瘤中频繁上调。我们还鉴定了一个与β-连环蛋白/TCF 7 L2复合物相关的远端增强子区域。进一步的分析表明，ODAM在细胞周期、DNA合成和细胞增殖的调节中起重要作用。这些数据可能有助于阐明这些癌症的主要分子机制。我们已经确定了牙源性成釉细胞相关基因（odontogenic ameloblast associated，ODAM）作为Wnt/β-catenin信号转导的新靶基因。在大多数肝母细胞瘤细胞以及一些肝细胞癌和结直肠癌细胞中其表达增强。ODAM表达升高与肿瘤细胞增殖相关。
The Wnt/β‐catenin signaling pathway plays a key role in development and carcinogenesis. Although some target genes of this signaling have been identified in various tissues and neoplasms, the comprehensive understanding of the target genes and their roles in the development of human cancer, including hepatoma and colorectal cancer remain to be fully elucidated. In this study, we searched for genes regulated by the Wnt signaling in liver cancer using HuH‐7 hepatoma cells. A comparison of the expression profiles between cells expressing an active form of mutant β‐catenin and cells expressing enhanced green fluorescent protein (EGFP) identified seven genes upregulated by the mutant β‐catenin gene (CTNNB1). Among the seven genes, we focused in this study on ODAM, odontogenic, ameloblast associated, as a novel target gene. Interestingly, its expression was frequently upregulated in hepatocellular carcinoma, colorectal adenocarcinoma, and hepatoblastoma. We additionally identified a distant enhancer region that was associated with the β‐catenin/TCF7L2 complex. Further analyses revealed that ODAM plays an important role in the regulation of the cell cycle, DNA synthesis, and cell proliferation. These data may be useful for clarification of the main molecular mechanism(s) underlying these cancers. We have identified odontogenic ameloblast associated (ODAM) as a novel target gene of the Wnt/ß‐catenin signaling. Its expression is augmented in the majority of hepatoblastoma cells, and some hepatocellular and colorectal carcinoma cells. Elevated ODAM expression is associated with the proliferation of tumor cells.
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影响因子：
30.8
作者：
Falck, J;Petrini, JHJ;Bartek, J
通讯作者：
Bartek, J
影响因子：
4.8
作者：
Filali, M;Cheng, NL;Engelhardt, JF
通讯作者：
Engelhardt, JF
影响因子：
5.3
作者：
Nakaya, Naoki;Hemish, Jill;Enikolopov, Grigori
通讯作者：
Enikolopov, Grigori
影响因子：
56.9
作者：
He, TC;Sparks, AB;Kinzler, KW
通讯作者：
Kinzler, KW
DOI：
10.1073/pnas.0607289103
发表时间：
2006-12-05
影响因子：
11.1
作者：
Jarvinen, Elina;Salazar-Ciudad, Isaac;Thesleff, Irma
通讯作者：
Thesleff, Irma