Abstract
BackgroundThe NIMA-related kinase 2 (NEK2) is a serine/threonine kinase that is involved in regulation of centrosome duplication and spindle assembly during mitosis. Dysregulation of these processes causes chromosome instability and aneuploidy, which are hallmark changes of many solid tumors. However, whether aberrant expression of NEK2 is associated with outcome of prostate cancer (PCa) patients remains to be determined.MethodsExpression of NEK2 in human PCa cells and primary PCa tissues was assessed by quantitative RT-PCR. Expression of NEK2 in human PCa cells was depleted with siRNA. Effects of the depletion on cell proliferation, survival, and tumorigenicity were assessed both in vitro with cell cultures and in vivo with subcutaneous implantation of xenografts. In silico analyses of the online Taylor dataset were carried out to determine whether the expression level of NEK2 correlated with the clinicopathological characteristics of prostate cancer.ResultsCompared with benign human prostatic epithelial cells and tissues, the expression of NEK2 was elevated in human PCa cells and primary PCa tissues. Depleting NEK2 expression inhibited human PCa cell proliferation in vitro and xenograft growth in vivo. Expression level of NEK2 in PCa positively correlated with the Gleason score and pathologic stage of the patient.ConclusionThe results suggest that overexpression of NEK2 has the potential to serve as a biomarker for PCa prognosis. Further validation with large sample pool is warrant.
Highlights
The NIMA-related kinase 2 (NEK2) is a serine/threonine kinase that is involved in regulation of centrosome duplication and spindle assembly during mitosis
We investigated expression patterns of NEK2 in tissue microarrays (TMAs) of human prostate cancer (PCa) and the effect of NEK2 depletion on cell proliferation in PCa cells
Depleting NEK2 expression reduces cell proliferation in PCa cells To determine whether human PCa cells had aberrant NEK2 expression at the mRNA level, quantitative realtime RT-PCR was performed to assess the expression of NEK2 in three human PCa and one benign human prostatic epithelial cell lines
Summary
The NIMA-related kinase 2 (NEK2) is a serine/threonine kinase that is involved in regulation of centrosome duplication and spindle assembly during mitosis. Dysregulation of these processes causes chromosome instability and aneuploidy, which are hallmark changes of many solid tumors. NEK2 is a constitutive active serine and threonine kinase that phosphorylates multiple proteins involved in centrosome duplication and cell cycle regulation. It binds to microtubules and is enriched in the centrosome, where it contributes to centrosome splitting during the G2/M phase of the cell cycle [9]. Expression of a kinase-dead mutant of NEK2 induces centrosome abnormalities and
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