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dc.contributor.authorHayward, Daniel G
dc.contributor.authorClarke, Robert B
dc.contributor.authorFaragher, Alison J
dc.contributor.authorPillai, Meenu R
dc.contributor.authorHagan, Iain M
dc.contributor.authorFry, Andrew M
dc.date.accessioned2009-08-21T11:25:10Z
dc.date.available2009-08-21T11:25:10Z
dc.date.issued2004-10-15
dc.identifier.citationThe centrosomal kinase Nek2 displays elevated levels of protein expression in human breast cancer. 2004, 64 (20):7370-6 Cancer Res.en
dc.identifier.issn0008-5472
dc.identifier.pmid15492258
dc.identifier.doi10.1158/0008-5472.CAN-04-0960
dc.identifier.urihttp://hdl.handle.net/10541/78148
dc.description.abstractAneuploidy 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.
dc.language.isoenen
dc.subjectCell Line Tumouren
dc.subjectBreast Canceren
dc.subject.meshAneuploidy
dc.subject.meshBreast
dc.subject.meshBreast Neoplasms
dc.subject.meshCarcinoma in Situ
dc.subject.meshCarcinoma, Ductal
dc.subject.meshCell Line, Tumor
dc.subject.meshCell Transformation, Neoplastic
dc.subject.meshHumans
dc.subject.meshImmunohistochemistry
dc.subject.meshProtein-Serine-Threonine Kinases
dc.subject.meshTransfection
dc.subject.meshUp-Regulation
dc.titleThe centrosomal kinase Nek2 displays elevated levels of protein expression in human breast cancer.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry, University of Leicester, Leicester, USA.en
dc.identifier.journalCancer Researchen
html.description.abstractAneuploidy 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.


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