PDZ-binding kinase/T-LAK cell-originated protein kinase, a putative cancer/testis antigen with an oncogenic activity in breast cancer
PDZ-binding kinase/T-LAK cell-originated protein kinase, a putative cancer/testis antigen with an oncogenic activity in breast cancer
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DOI：
10.1158/0008-5472.can-06-1601
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发表时间：
2006-09-15
期刊：
影响因子：
11.2
通讯作者：
Katagiri, Toyomasa
中科院分区：
文献类型：
--
作者：
Park, Jae-Hyun;Lin, Meng-Lay;Katagiri, Toyomasa
乳腺癌是女性最常见的癌症之一。为了发现适用于开发新型乳腺癌疗法的分子靶点，我们之前对 81 种乳腺癌进行了全基因组表达谱分析，发现了数十种在乳腺癌细胞中高度且普遍上调的基因。其中，我们重点关注编码 PDZ 结合激酶/T-LAK 细胞源蛋白激酶 (PBK/TOPK) 的一个基因，包括一个激酶结构域。使用正常人体器官、乳腺癌组织和癌细胞系的 mRNA 进行 Northern 印迹分析表明该分子是一种新型癌症/睾丸抗原。小干扰 RNA 减少 PBKITOPK 表达导致细胞生长显着抑制，这可能是由于细胞因子过程功能障碍所致。使用抗 PBK/TOPK 抗体进行的免疫细胞化学分析表明 PBK/TOPK 在有丝分裂的早期步骤中发挥着关键作用。 PBK/ TOPK 在体外和体内均可磷酸化组蛋白 H3 Ser(10)，并通过组蛋白 H3 修饰介导其促生长作用。由于 PBK/TOPK 是癌症/睾丸抗原，其激酶功能可能与其致癌活性有关，因此我们建议 PBK/TOPK 成为乳腺癌治疗的一个有前途的分子靶点。
Breast cancer is one of the most common cancers among women. To discover molecular targets that are applicable for development of novel breast cancer therapy, we previously did genome-wide expression profile analysis of 81 breast cancers and found dozens of genes that were highly and commonly up-regulated in breast cancer cells. Among them, we here focused on one gene that encodes PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK), including a kinase domain. Northern blot analyses using mRNAs of normal human organs, breast cancer tissues, and cancer cell lines indicated this molecule to be a novel cancer/testis antigen. Reduction of PBKITOPK expression by small interfering RNA resulted in significant suppression of cell growth probably due to dysfunction in the cytokinetic process. Immunocytochemical analysis with anti-PBK/TOPK antibody implicated a critical role of PBK/TOPK in an early step of mitosis. PBK/ TOPK could phosphorylate histone H3 at Ser(10) in vitro and in vivo, and mediated its growth-promoting effect through histone H3 modification. Because PBK/TOPK is the cancer/ testis antigen and its kinase function is likely to be related to its oncogenic activity, we suggest PBK/TOPK to be a promising molecular target for breast cancer therapy.