Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas

Federica Barbagallo, Maria P. Paronetto, Renato Franco, Paolo Chieffi, Susanna Dolci, Andrew M. Fry, Raffaele Geremia, Claudio Sette

Research output: Contribution to journalArticle

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 immunok-inase 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 sternness 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.

Original languageEnglish
Pages (from-to)431-441
Number of pages11
JournalJournal of Pathology
Volume217
Issue number3
DOIs
Publication statusPublished - Feb 2009

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Centrosome
Seminoma
Phosphotransferases
Germ Cells
Testis
Up-Regulation
Chromosome Segregation
Spindle Apparatus
Aneuploidy
Cell Nucleus
Protein Kinases
Immunohistochemistry
Cell Line
Proteins

Keywords

  • Centrosome
  • Germ cells
  • Nek2
  • Neoplastic transformation
  • Seminomas
  • Testis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas. / Barbagallo, Federica; Paronetto, Maria P.; Franco, Renato; Chieffi, Paolo; Dolci, Susanna; Fry, Andrew M.; Geremia, Raffaele; Sette, Claudio.

In: Journal of Pathology, Vol. 217, No. 3, 02.2009, p. 431-441.

Research output: Contribution to journalArticle

Barbagallo, Federica ; Paronetto, Maria P. ; Franco, Renato ; Chieffi, Paolo ; Dolci, Susanna ; Fry, Andrew M. ; Geremia, Raffaele ; Sette, Claudio. / Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas. In: Journal of Pathology. 2009 ; Vol. 217, No. 3. pp. 431-441.
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