Department of Microbiology, Chungnam National University, Daejeon 305-764, Korea.
Mol Cell Biochem. 2010 Jul;340(1-2):161-7. doi: 10.1007/s11010-010-0413-x. Epub 2010 Feb 24.
In order to discover previously unidentified cancer-associated genes, we analyzed genome-wide differences in gene expression between tumor biopsies and normal tissues. Among those differentially regulated genes, we identified Sharpin (Shank-associated RH domain-interacting protein) as a commonly up-regulated gene in multiple human cancer types. Although rat Sharpin is reported to interact with Shank1, a multidomain scaffold protein localized in postsynaptic densities, its exact roles are unknown. Whereas human Sharpin homologue was primarily localized in the cytosol of cultured cells, they were detected in both cytosol and nucleus of the cells from ovarian and liver cancer tissues using immunohistochemical staining. In addition, Chinese ovary hamster cells over-expressing Sharpin exhibited enhanced cancer-specific phenotypes in multiple in vitro tumor assays. Taken together, the results suggest that Sharpin is not an inert scaffold protein, but may play tumor-associated roles during cancer biogenesis.
为了发现以前未被识别的与癌症相关的基因,我们分析了肿瘤活检组织和正常组织之间的全基因组基因表达差异。在这些差异调节的基因中,我们发现 Sharpin(Shank 相关 RH 结构域相互作用蛋白)是多种人类癌症类型中普遍上调的基因。虽然已经报道大鼠 Sharpin 与 Shank1 相互作用,Shank1 是一种定位于突触后密度的多结构域支架蛋白,但它的确切作用尚不清楚。尽管人源 Sharpin 同源物主要定位于培养细胞的细胞质中,但使用免疫组织化学染色,在卵巢癌和肝癌组织的细胞中既检测到细胞质,也检测到细胞核中存在 Sharpin。此外,过表达 Sharpin 的中国仓鼠卵巢细胞在多种体外肿瘤检测中表现出增强的癌症特异性表型。综上所述,这些结果表明 Sharpin 不是一种无活性的支架蛋白,而是在癌症发生过程中可能发挥与肿瘤相关的作用。