title: 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.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
authors.forename: Meng-Lay
authors.initials: ML
authors.lastname: Lin
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nishidate
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Katagiri
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020929:Mitogen-Activated Protein Kinase Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D006657:Histones; D017346:Protein Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase