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.

Barbagallo, F., Paronetto, M., Franco, R., Chieffi, P., DOLCI IANNINI, S., Fry, A., et al. (2009). Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas. JOURNAL OF PATHOLOGY, 217(3), 431-441 [10.1002/path.2471].

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

DOLCI IANNINI, SUSANNA;GEREMIA, RAFFAELE;SETTE, CLAUDIO
2009-02-01

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.
feb-2009
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/16 - ANATOMIA UMANA
English
Con Impact Factor ISI
Cell Nucleus; Immunoprecipitation; Male; Protein-Serine-Threonine Kinases; Gene Expression Regulation, Neoplastic; Seminoma; Microscopy, Fluorescence; Testicular Neoplasms; Animals; Humans; Cell Line, Tumor; Up-Regulation; Mice
Barbagallo, F., Paronetto, M., Franco, R., Chieffi, P., DOLCI IANNINI, S., Fry, A., et al. (2009). Increased expression and nuclear localization of the centrosomal kinase Nek2 in human testicular seminomas. JOURNAL OF PATHOLOGY, 217(3), 431-441 [10.1002/path.2471].
Barbagallo, F; Paronetto, M; Franco, R; Chieffi, P; DOLCI IANNINI, S; Fry, A; Geremia, R; Sette, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/28052
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