RUNX3 protein is overexpressed in human basal cell carcinomas
RUNX3 protein is overexpressed in human basal cell carcinomas
复制标题
DOI：
10.1038/sj.onc.1209739
复制
发表时间：
2006-12-07
期刊：
影响因子：
8
通讯作者：
Ito, Y.
中科院分区：
文献类型：
--
作者：
Salto-Tellez, M.;Peh, B. K.;Ito, Y.
基底细胞癌（BCC）是最常见的皮肤恶性肿瘤，总是与Sonic Hedgehog（Shh）信号通路的失调有关。因此，BCC代表了研究Shh途径与其他基因和途径相互作用的独特模型。我们构建了75对BCC和正常皮肤的组织微阵列（TMA），并分别分析了无翼Int（Wnt）和骨形态发生蛋白/转化生长因子β通路的核效应子β-连环蛋白和RUNX 3的表达。与以前的报道一致，我们观察到BCC中β-连环蛋白的不同亚细胞表达模式，其中31例（41%）显示核积聚。相比之下，通过TMA测试的所有BCC病例均显示RUNX 3蛋白在癌细胞核中均匀过表达。通过Western印迹和DNA测序分析表明，过表达的蛋白质是正常的和全长的，在编码区不含突变，暗示RUNX 3是某些人类癌症中的癌基因。我们的研究结果表明，虽然Wnt信号的失调可能有助于一个子集的BCC的发病机制，RUNX 3似乎是一个普遍的下游介质的组成性活跃的Shh途径在BCC。
Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of beta-catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor-beta pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of beta-catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.