Kanehira M, Harada Y, Takata R, Shuin T, Miki T, Fujioka T, Nakamura Y, Katagiri T
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
Oncogene. 2007 Sep 27;26(44):6448-55. doi: 10.1038/sj.onc.1210466. Epub 2007 Apr 23.
In an attempt to disclose mechanisms of bladder carcinogenesis and discover novel target molecules for development of treatment, we applied a cDNA microarray to screen genes that were significantly transactivated in bladder cancer cells. Among the upregulated genes, we here focused on a novel gene, (DEPDC1) DEP domain containing 1, whose overexpression was confirmed by northern blot and immunohistochemical analyses. Immunocytochemical staining analysis detected strong staining of endogenous DEPDC1 protein in the nucleus of bladder cancer cells. Since DEPDC1 expression was hardly detectable in any of 24 normal human tissues we examined except the testis, we considered this gene-product to be a novel cancer/testis antigen. Suppression of DEPDC1 expression with small-interfering RNA significantly inhibited growth of bladder cancer cells. Taken together, these findings suggest that DEPDC1 might play an essential role in the growth of bladder cancer cells, and would be a promising molecular-target for novel therapeutic drugs or cancer peptide-vaccine to bladder cancers.
为了揭示膀胱癌发生的机制并发现用于治疗开发的新靶分子,我们应用cDNA微阵列筛选在膀胱癌细胞中显著反式激活的基因。在这些上调基因中,我们重点关注一个新基因,即含DEP结构域1(DEPDC1),其过表达通过Northern印迹和免疫组织化学分析得以证实。免疫细胞化学染色分析检测到膀胱癌细胞核内有内源性DEPDC1蛋白的强染色。由于在我们检测的24种正常人体组织中,除睾丸外,几乎检测不到DEPDC1的表达,我们认为该基因产物是一种新的癌/睾丸抗原。用小干扰RNA抑制DEPDC1的表达可显著抑制膀胱癌细胞的生长。综上所述,这些发现表明DEPDC1可能在膀胱癌细胞的生长中起重要作用,并且有望成为新型治疗药物或膀胱癌癌肽疫苗的分子靶点。