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使用DNA微阵列对过表达Nm23-H2的CAL 27细胞进行基因表达谱分析。

Gene expression profiling of Nm23-H2 overexpressing CAL 27 cells using DNA microarray.

作者信息

Herak Bosnar M, Bago R, Konjevoda P, Pavelić J

机构信息

Rudjer Bosković Institute, Division of Molecular Medicine, Zagreb, Croatia.

出版信息

Neoplasma. 2008;55(5):447-54.

Abstract

Nm23-H1/NDPKA and Nm23-H2/NDPKB belong to a large family of NDP kinases, group of structurally and functionally closely related enzymes. The Nm23/NDPs are known to catalyse the transfer of terminal phosphates from ATP to other NTPs and dNTPs. Besides their role in the maintenance of the cells NTP pool the nm23 genes/proteins are known to have additional different biological functions, the most important being its metastasis suppressor activity. The complete picture of roles, actions and targets of nm23 genes/proteins is yet to be discovered. Our goal was to identify the downstream targets of Nm23-H2 by subjecting Nm23-H2 overexpressing CAL 27 cells (oral squamous cell carcinoma of the tongue) to microarray analysis. Using this powerful technology we identified genes, groups of genes and signalling pathways that could be clustered into several groups: apoptosis related genes, cell cycle and DNA damage, TGFbeta (transforming growth factor beta) signalling pathway and related molecules, WNT signalling pathway, differentiation and epithelial structural and related molecules, cell adhesion, metalloproteinases and their inhibitors, vesicular transport related molecules, proteasome associated, ubiquitin mediated proteolysis and several metabolic pathways. Based on these results we suggest that nm23-H2 might have an important role in oral squamous cell carcinoma which is to be confirmed by future studies.

摘要

Nm23-H1/NDPKA和Nm23-H2/NDPKB属于NDP激酶的一个大家族,这是一组结构和功能密切相关的酶。已知Nm23/NDPs能催化ATP末端磷酸基团转移至其他NTP和dNTP。除了在维持细胞NTP库中的作用外,nm23基因/蛋白还具有其他不同的生物学功能,其中最重要的是其转移抑制活性。nm23基因/蛋白的作用、行为和靶点的全貌还有待发现。我们的目标是通过对过表达Nm23-H2的CAL 27细胞(舌部口腔鳞状细胞癌)进行微阵列分析,来鉴定Nm23-H2的下游靶点。利用这项强大的技术,我们鉴定出了可分为几组的基因、基因群和信号通路:凋亡相关基因、细胞周期和DNA损伤、TGFβ(转化生长因子β)信号通路及相关分子、WNT信号通路、分化及上皮结构和相关分子、细胞黏附、金属蛋白酶及其抑制剂、囊泡运输相关分子、蛋白酶体相关、泛素介导的蛋白水解以及几条代谢途径。基于这些结果,我们认为nm23-H2可能在口腔鳞状细胞癌中发挥重要作用,这还有待未来研究证实。

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