Oncogenic role of NALP7 in testicular seminomas.
To isolate novel molecular targets for treatment of testicular germ cell tumor (TGCT), we performed genome-wide expression profile analysis of testicular seminomas using a cDNA microarray. We here report identification of NACHT, leucine-rich repeat and PYD containing 7 (NALP7 ), that was significantly transactivated in testicular seminomas. Subsequent semi-quantitative RT-PCR and northern blot analyses confirmed an approximately 3.3-kb transcript that was expressed exclusively in testis, although the expression level of this gene in normal testis was much lower than in tumor cells, suggesting an important role of this gene in germ-cell proliferation. Immunohistochemical analysis using anti-NALP7 polyclonal antibody detected the endogenous NALP7 protein in the cytoplasm of embryonal carcinoma cells and testicular seminoma tissues. Transfection of small interfering RNA (siRNA) for NALP7 significantly reduced the NALP7 expression and resulted in growth suppression of testicular germ-cell tumors. These findings imply that NALP7 may play a crucial role in cell proliferation, as well as testicular tumorigenesis, and it appears to be a promising candidate for development of targeted therapy for TGCTs.
Okada
Koichi
K
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Hirota
Eiji
E
Mizutani
Yoichi
Y
Fujioka
Tomoaki
T
Shuin
Taro
T
Miki
Tsuneharu
T
Nakamura
Yusuke
Y
Katagiri
Toyomasa
T
D000818:Animals; D016466:CHO Cells; D018236:Carcinoma, Embryonal / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D006224:Cricetinae; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000276:immunology / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018239:Seminoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D015398:Signal Transduction; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D013737:Testis / Q000378:metabolism; D015533:Transcriptional Activation
D047908:Intracellular Signaling Peptides and Proteins; C476731:NLRP12 protein, human; D034741:RNA, Small Interfering; D011994:Recombinant Proteins