PDZ-binding kinase/T-LAK cell-originated protein kinase, a putative cancer/testis antigen with an oncogenic activity in breast cancer

Abstract

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 PBK/TOPK 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 Ser10 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. ©2006 American Association for Cancer Research.