The centrosomal kinase Nek2 displays elevated levels of protein expression in human breast cancer.
Aneuploidy and chromosome instability are common abnormalities in human cancer. Loss of control over mitotic progression, multipolar spindle formation, and cytokinesis defects are all likely to contribute to these phenotypes. Nek2 is a cell cycle-regulated protein kinase with maximal activity at the onset of mitosis that localizes to the centrosome. Functional studies have implicated Nek2 in regulation of centrosome separation and spindle formation. Here, we present the first study of the protein expression levels of the Nek2 kinase in human cancer cell lines and primary tumors. Nek2 protein is elevated 2- to 5-fold in cell lines derived from a range of human tumors including those of cervical, ovarian, breast, prostate, and leukemic origin. Most importantly, by immunohistochemistry, we find that Nek2 protein is significantly up-regulated in preinvasive in situ ductal carcinomas of the breast as well as in invasive breast carcinomas. Finally, by ectopic expression of Nek2A in immortalized HBL100 breast epithelial cells, we show that increased Nek2 protein leads to accumulation of multinucleated cells with supernumerary centrosomes. These data highlight the Nek2 kinase as novel potential target for chemotherapeutic intervention in breast cancer.
Hayward
Daniel G
DG
Department of Biochemistry, University of Leicester, Leicester, USA.
Clarke
Robert B
RB
Faragher
Alison J
AJ
Pillai
Meenu R
MR
Hagan
Iain M
IM
Fry
Andrew M
AM
D000782:Aneuploidy; D001940:Breast / Q000378:metabolism / Q000502:physiology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D002278:Carcinoma in Situ / Q000201:enzymology / Q000235:genetics; D044584:Carcinoma, Ductal / Q000201:enzymology / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation
C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; D017346:Protein Serine-Threonine Kinases