title: Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas.
abstract: Protein kinases that regulate the centrosome cycle are often aberrantly controlled in neoplastic cells. Changes in their expression or activity can lead to perturbations in centrosome duplication, potentially leading to chromosome segregation errors and aneuploidy. Testicular germ cell tumours (TGCTs) are characterized by amplification of centrosomes through unknown mechanisms. Herein, we report that Nek2, a centrosomal kinase required for centrosome disjunction and formation of the mitotic spindle, is up-regulated in human testicular seminomas as compared to control testes or other types of testicular germ cell tumours. In addition, Nek2 activity is also increased in human seminomas, as demonstrated by immunokinase assays. Analysis by immunohistochemistry indicated that Nek2 is prevalently localized in the nucleus of neoplastic cells of primary human seminomas. Such nuclear localization and the up-regulation of Nek2 protein were also observed in the Tcam-2 seminoma cell line. We demonstrate that nuclear localization of Nek2 is a feature of the more undifferentiated germ cells of mouse testis and correlates with expression of the stemness markers OCT4 and PLZF. These studies suggest that up-regulation of Nek2 is a frequent event in human seminomas and that this may participate in the onset or progression of neoplastic transformation through deregulation of centrosome duplication and/or nuclear events in germ cells.
authors.affiliation: Department of Public Health and Cell Biology, University of Rome Tor Vergata, 00133 Rome, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Barbagallo
authors.forename: Maria P
authors.initials: MP
authors.lastname: Paronetto
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Paolo
authors.initials: P
authors.lastname: Chieffi
authors.forename: Susanna
authors.initials: S
authors.lastname: Dolci
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Fry
authors.forename: Raffaele
authors.initials: R
authors.lastname: Geremia
authors.forename: Claudio
authors.initials: C
authors.lastname: Sette
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008856:Microscopy, Fluorescence; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics*; D018239:Seminoma / Q000235:genetics*; D013736:Testicular Neoplasms / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases