Silva Fabio Pittella, Hamamoto Ryuji, Nakamura Yusuke, Furukawa Yoichi
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Neoplasia. 2005 Apr;7(4):348-55. doi: 10.1593/neo.04544.
In an attempt to disclose mechanisms of hepatocarcinogenesis and discover novel target molecules for the diagnosis and treatment of hepatocellular carcinomas (HCCs), we previously analyzed expression profiles of HCC tissues by means of human cDNA microarray. Among the genes upregulated in tumor tissues compared with their nontumor counterparts, we focused on a novel gene, termed WDRPUH, and characterized its biologic function. WDRPUH encodes a predicted 620-amino acid protein containing 11 highly conserved WD40-repeat domains. Multiple-tissue Northern blot analysis revealed its specific expression in the testis among 16 normal tissues examined. Transfection of plasmids designed to express WDRPUH-specific siRNA significantly reduced its expression in HCC cells and resulted in growth suppression of transfected cells. Interestingly, we found that WDRPUH associated with HSP70, proteins of the chaperonin-containing TCP-1 (CCT1) complex, as well as BRCA2. These findings have disclosed a novel insight into hepatocarcinogenesis and suggested that WDRPUH may be a molecular target for the development of new strategies to treat HCCs.
为了揭示肝癌发生的机制并发现用于肝细胞癌(HCC)诊断和治疗的新靶分子,我们之前通过人cDNA微阵列分析了HCC组织的表达谱。在肿瘤组织中相对于非肿瘤对应组织上调的基因中,我们聚焦于一个名为WDRPUH的新基因,并对其生物学功能进行了表征。WDRPUH编码一种预测的含620个氨基酸的蛋白质,该蛋白质含有11个高度保守的WD40重复结构域。多组织Northern印迹分析显示,在所检测的16种正常组织中,它在睾丸中特异性表达。转染设计用于表达WDRPUH特异性siRNA的质粒可显著降低其在HCC细胞中的表达,并导致转染细胞的生长抑制。有趣的是,我们发现WDRPUH与HSP70、含伴侣蛋白的TCP-1(CCT1)复合物的蛋白质以及BRCA2相关。这些发现揭示了对肝癌发生的新见解,并表明WDRPUH可能是开发治疗HCC新策略的分子靶点。