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.
Highlights
Renal cell carcinoma (RCC) is the most lethal of the common urological cancers with 338.000 new cases and 144.000 deaths registered worldwide in 2012 [1]
We examined a total of 155 patients with different subtypes of RCC and oncocytoma
Quantitative RT-PCR data from 97 clear cell renal cell carcinoma (ccRCC) were generated from another study [24]
Summary
Renal cell carcinoma (RCC) is the most lethal of the common urological cancers with 338.000 new cases and 144.000 deaths registered worldwide in 2012 [1]. The most frequent subtype is the clear cell renal cell carcinoma (ccRCC), which comprises 75-80% of all RCCs. The papillary carcinoma (PRCC, 10% of RCC), chromophobic carcinoma (ChRCC, 5% of RCC) and collecting duct carcinoma (2% of RCC) are the other main subtypes. Used clinicopathological parameters, such as TNM staging and nuclear Fuhrman grade, provide robust prognostic information. They cannot accurately predict a reliable outcome for RCC since similar TNM stage and nuclear grade may have very different outcomes
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