Examination of CK2α and NF-κB p65 expression in human benign prostatic hyperplasia and prostate cancer tissues

Abstract

Protein kinase CK2 plays a critical role in cell growth, proliferation, and suppression of cell death. CK2 is overexpressed, especially in the nuclear compartment, in the majority of cancers, including prostate cancer (PCa). CK2-mediated activation of transcription factor nuclear factor kappa B (NF-κB) p65 is a key step in cellular proliferation, resulting in translocation of NF-κB p65 from the cytoplasm to the nucleus. As CK2 expression and activity are also elevated in benign prostatic hyperplasia (BPH), we sought to increase the knowledge of CK2 function in benign and malignant prostate by examination of the relationships between nuclear CK2 and nuclear NF-κB p65 protein expression. The expression level and localization of CK2α and NF-κB p65 proteins in PCa and BPH tissue specimens was determined. Nuclear CK2α and NF-κB p65 protein levels are significantly higher in PCa compared with BPH, and these proteins are positively correlated with each other in both diseases. Nuclear NF-κB p65 levels correlated with Ki-67 or with cytoplasmic NF-κB p65 expression in BPH, but not in PCa. The findings provide information that combined analysis of CK2α and NF-κB p65 expression in prostate specimens relates to the disease status. Increased nuclear NF-κB p65 expression levels in PCa specifically related to nuclear CK2α levels, indicating a possible CK2-dependent relationship in malignancy. In contrast, nuclear NF-κB p65 protein levels related to both Ki-67 and cytoplasmic NF-κB p65 levels exclusively in BPH, suggesting a potential separate impact for NF-κB p65 function in proliferation for benign disease as opposed to malignant disease.

CK2 in Cancer: Cellular and Biochemical Mechanisms and Potential Therapeutic Target

“…Rationale for CK2 inhibition in prostate cancer: CK2 protein levels and activity are deregulated in prostate cancer and prostate cancer-derived cells. Human benign prostatic hyperplasia (BPH; n = 31) and prostate cancer ( n = 30) tissue sections had higher staining for CK2α and NF-κB compared to normal prostate tissue specimens [ 137 ]. Furthermore, CK2α staining in sections is higher in malignant compared to normal human prostate glandular cells.…”

“…CK2 is overexpressed in many cancers and often overexpression is associated with worse prognosis, although the opposite may be true in some cancer types as reviewed above [ 19 ]. CK2 can be used as a diagnostic and prognostic marker in certain malignancies, such as prostate cancer [ 19 , 137 ]. However, we the potential for CK2 expression as a prognostic and diagnostic marker could be greater as only a few studies analyze all three CK2 proteins, CK2 activity and localization.…”

CK2 Molecular Targeting—Tumor Cell-Specific Delivery of RNAi in Various Models of Cancer

“…This raises a question as to the nature of functionality of CK2 in prostatic cancer (PCa) versus BPH. To address this issue, we examined the combined expression of CK2α and NFκB p65 in PCa and BPH, considering that both are elevated in each of these diseases and that NFκB p65 is a known substrate of CK2α [ 33 , 34 ]. We thus wanted to determine if there was a differential expression of CK2α and NFκB p65 that may provide a means of distinction between the two diseases.…”

“…Interestingly, nuclear NFκB p65 levels correlated with cytoplasmic NFκB p65 as well as Ki-67 signals in BPH, but not in PCa. It is noteworthy that these various correlations were apparent at the protein level and require the ability to determine nuclear and cytoplasmic localization of the signals [ 33 ]. Together, these observations suggest that with respect to their combined activity CK2 and NFκB have different modes of functionality in the biology of benign prostate growth and malignancy.…”

Protein Kinase CK2, a Potential Therapeutic Target in Carcinoma Management

“…In conclusion, CK2 is overexpressed in many carcinomas and often associated with poor prognosis (but not in all cases). CK2 has been used as a diagnostic and prognostic marker for certain malignancies such as prostate carcinoma (Ortega et al, 2014;Qaiser et al, 2016). Further research about CK2 activity levels of all three CK2 subunits and their localizations may explore greater potential of CK2 as a diagnostic and prognostic marker.…”