Oncotarget

Research Papers:

Nuclear localization of the CK2α-subunit correlates with poor prognosis in clear cell renal cell carcinoma

Maj Rabjerg _, Barbara Guerra, Aida Oliván-Viguera, Minne Line Nedergaard Mikkelsen, Ralf Köhler, Olaf-Georg Issinger and Niels Marcussen

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Oncotarget. 2017; 8:1613-1627. https://doi.org/10.18632/oncotarget.13693

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Abstract

Maj Rabjerg1, Barbara Guerra2, Aida Oliván-Viguera3, Minne Line Nedergaard Mikkelsen1, Ralf Köhler3, Olaf-Georg Issinger2, Niels Marcussen1

1Department of Pathology, Odense University Hospital, DK-5000 Odense, Denmark

2Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark

3Aragon Agency for Research and Development (ARAID), IACS, IIS Aragon, 50009 Zaragoza, Spain

Correspondence to:

Maj Rabjerg, email: [email protected]

Keywords: renal cancer, protein kinase CK2, CK2 subunits, CK2-targeted therapy, CX-4945

Received: April 25, 2016    Accepted: November 11, 2016    Published: November 29, 2016

ABSTRACT

Protein kinase CK2α, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2α expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC). Also the kinase activity of CK2 was significantly increased in ccRCC compared to normal renal cortex. Nuclear protein expression of CK2α correlated in univariate analysis with poor Progression Free Survival (HR = 8.11, p = 0.016). Functional analyses (cell proliferation assay) revealed an inhibitory effect of Caki-2 cell growth following CK2 inhibition with CX-4945. Our results suggest that CK2α promotes migration and invasion of ccRCC and therefore could serve as a novel prognostic biomarker and molecular therapeutic target in this type of cancer.


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