Identification of PDZK4, a novel human gene with PDZ domains, that is upregulated in synovial sarcomas.
In an earlier study designed to investigate molecular mechanisms of carcinogenesis in synovial sarcomas (SSs), we applied a cDNA microarray to detect human genes with significantly increased expression in SS cells. Among the genes selected in this way, we identified a novel transcript, subsequently designated PDZK4 (PDZ domain-containing 4), that was specifically upregulated in all of the 13 SS cases we examined. On Northern blots of normal human tissues, the PDZK4 transcript was expressed only in fetal brain. Immunocytochemical staining of transfected COS7 cells showed that the PDZK4 gene product localized mainly under the plasma membrane. Treatment of human SS cells with small interfering RNA (siRNA) inhibited the expression of PDZK4 and resulted in the suppression of tumor-cell growth. Induction of exogenous PDZK4 expression promoted growth of T98G and COS7 cells in which no endogenous expression of PDZK4 was observed. Taken together, these findings strongly suggest that inappropriate expression of PDZK4 might play an important role in the proliferation of SS cells and that the gene might be a suitable molecular target for designing of novel drugs to treat SS patients.
Nagayama
Satoshi
S
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Iiizumi
Megumi
M
Katagiri
Toyomasa
T
Toguchida
Junya
J
Nakamura
Yusuke
Y
D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D041321:Chromosomes, Human, X; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D009363:Neoplasm Proteins; C488622:PDZD4 protein, human; D034741:RNA, Small Interfering