Nuclear casein kinase 2 (CK‐2) activity in human normal, benign hyperplastic, and cancerous prostate

Abstract

In previous work, we had observed that chromatin-associated nonhistone protein phosphorylation, catalyzed by intrinsic protein kinase reaction in chromatin preparations from human benign prostatic hyperplasia (BPH) prostate samples was markedly elevated, compared with the normal prostate chromatin samples [Rayan et al: Cancer Res 45:2277-2282, 1985]. The properties of this protein kinase reaction were suggestive of the involvement of casein kinase(s). By employing the specific synthetic substrate for casein kinase 2 (CK-2) for assays in cellular fractions, we have shown that this protein kinase is present in human prostate chromatin. Its activity is increased in BPH chromatin by about 25-fold, as compared with its activity in the normal prostate chromatin. This suggests that CK-2 is a possible mediator of the enhanced phosphorylation of chromosomal proteins in BPH chromatin. By comparison, CK-2 activity in chromatin preparations from prostatic carcinoma samples was markedly less elevated than that of the BPH chromatin. Immunohistochemical analysis of the enzyme in human frozen sections of prostate tissue samples showed that the enzyme immunostaining was diffuse in the cytoplasm, but more intense in the nucleus, especially in the nucleoli. In general, the staining corresponded with the enzymic data. However, sections from prostatic carcinoma samples appeared to show differential staining, depending on the Gleason's grade of the sample. The samples with higher Gleason's grade showed less intense immunostain in the nucleus, compared with samples of lower Gleason's grade. Further, regions of sections in samples with higher Gleason's grade did not show any immunostaining. These differences in the characteristics of CK-2 expression in prostatic carcinoma samples may be potentially significant, but need to be evaluated further for their significance to the pathobiology of prostatic neoplasia.

NKX3.1 Is Regulated by Protein Kinase CK2 in Prostate Tumor Cells

“…Interestingly, while total CK2 activity increases in prostate tumors, the level of nuclear CK2 decreases in prostate tumor cells, although the antibody used in this study did not distinguish between CK2␣ and CK2␣Ј (60). However, given that NKX3.1 is predominantly a nuclear protein, this observation is consistent with a model wherein diminished free CK2␣Ј expression could account, at least in part, for the epigenetic loss of NKX3.1 expression observed in many prostate tumors.…”

“…In this scenario, CK2 activity would be predicted to be diminished in prostate tumor cells compared to normal prostate epithelial cells. In fact, using a peptide substrate to measure total CK2 activity in tumor samples, the level of CK2 has been reported to be significantly increased in prostate cancer cases (60). These observations would appear to be at odds with the predicted effect of CK2 on NKX3.1 expression.…”

Protein kinase CK2 – A key suppressor of apoptosis

“…Experimental transgenic mouse models of neoplasia in which altered CK2 signal served as a double transgene have provided significant support to this notion (e.g., Kelliher et al, 1996;Xu et al, 1999). The presence of elevated CK2 in cancer appears to correlate with the pathological status of the cancer and may serve as a prognostic marker (Yenice et al, 1994;Gapany et al, 1995;Faust et al, 1996;Faust et al, 1999;Piazza et al, 2006;Laramas et al, 2007). Although CK2 is present ubiquitously in all cells, it is noteworthy that its distribution in the normal versus cancer cells is distinct.…”

Phosphorylation regulates the stability of the regulatory CK2β subunit

“…Accordingly, alterations in CK2 levels have been observed in leukemic cells and in tumors. For example, increased levels of CK2 are observed in a variety of tumor cells including cancer cells derived from head and neck (Faust et al, 1996), prostate (Yenice et al, 1994), lung (Daya-Makin et al, 1994), kidney (Stalter et al, 1994) and breast (LandesmanBollag et al, 2001). Dramatic elevations in CK2 are also observed in the lymphocytes of parasite-infected cattle where the lymphocytes exhibited lymphoblastic appearance and tumor-forming ability in mice (ole-Moi Yoi et al, 1993).…”