Oncogenic role of MPHOSPH1, a cancer-testis antigen specific to human bladder cancer.
To disclose the molecular mechanism of bladder cancer, the second most common genitourinary tumor, we had previously done genome-wide expression profile analysis of 26 bladder cancers by means of cDNA microarray representing 27,648 genes. Among genes that were significantly up-regulated in the majority of bladder cancers, we here report identification of M-phase phosphoprotein 1 (MPHOSPH1) as a candidate molecule for drug development for bladder cancer. Northern blot analyses using mRNAs of normal human organs and cancer cell lines indicated this molecule to be a novel cancer-testis antigen. Introduction of MPHOSPH1 into NIH3T3 cells significantly enhanced cell growth at in vitro and in vivo conditions. We subsequently found an interaction between MPHOSPH1 and protein regulator of cytokinesis 1 (PRC1), which was also up-regulated in bladder cancer cells. Immunocytochemical analysis revealed colocalization of endogenous MPHOSPH1 and PRC1 proteins in bladder cancer cells. Interestingly, knockdown of either MPHOSPH1 or PRC1 expression with specific small interfering RNAs caused a significant increase of multinuclear cells and subsequent cell death of bladder cancer cells. Our results imply that the MPHOSPH1/PRC1 complex is likely to play a crucial role in bladder carcinogenesis and that inhibition of the MPHOSPH1/PRC1 expression or their interaction should be novel therapeutic targets for bladder cancers.
Kanehira
Mitsugu
M
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Katagiri
Toyomasa
T
Shimo
Arata
A
Takata
Ryo
R
Shuin
Taro
T
Miki
Tsuneharu
T
Fujioka
Tomoaki
T
Nakamura
Yusuke
Y
D000818:Animals; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D016547:Kinesins; D051379:Mice; D041681:NIH 3T3 Cells; D009857:Oncogenes; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000628:therapy
D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C438388:KIF20B protein, human; D016547:Kinesins