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.

Casein kinase 2 (CK-2) is a ubiquitous messenger-independent protein serine/threonine kinase that has been implicated in growth control. We have studied the activity and subcelular location of CK-2 in adult rat ventral prostate in relation to androgen withdrawal and administration. Androgen deprivation by castration results in a faster decline in CK-2 activity associated with prostatic nuclei than that in the cytosol. Nuclear CK-2 associated with chromatin is reduced at an even greater rate than that in the total nucleus. Reversal of these events by administration of a single dose of 5a-dihydrotestosterone to adult rats castrated 144 hr previously was accompanied by a differential early enhancement of chromatin-associated CK-2 activity, with a concomitant decrease in the CK-2 activity present in the cytosol. Changes in the nuclear CK-2 activity correlated with the immunostainable enzyme protein in the nucleus. We propose that androgens evoke translocation of CK-2 from the cytoplasm to the nucleus (nucleoplasm) where its enhanced association with the chromatin constituents takes place. Conversely, withdrawal of circulating androgens due to castration evokes a dissociation of CK-2 from chromatin and eventual translocation of nucleoplasmic CK-2 to the cytoplasm. Modulations in the association of CK-2 with nuclear chromatin may represent an important mechanism of post-transcriptional regulation of nuclear CK-2 in relation to androgen action in the prostate.Protein phosphorylation/dephosphorylation represents a major mechanism of mediation of cellular functions. The vast family ofknown protein kinases catalyzes phosphorylation of a multitude of proteins in the cell in response to various stimuli. Although cellular regulation of certain protein kinases is achieved through second messengers, the control mechanisms for the regulation of protein kinases that are not activated by any known second messenger are generally not well understood (1, 2). Casein kinases are a group of messenger-independent protein serine/threonine kinases found ubiquitously in eukaryotic cells. Casein kinase 1 (CK-1) and casein kinase 2 (CK-2), isolated from nuclear and cytosolic sources, have been well characterized. CK-2 is composed of three subunits of 42, 38, and 28 kDa, existing as a, a', and 32 configuration. Much work has implicated it in the phosphorylation of various cellular protein substrates, such as nuclear nonhistone proteins, certain oncoproteins, RNA polymerases, topoisomerases, steroid receptors, various factors involved in protein synthesis machinery, etc., leading to the proposal that CK-2 plays a role in cell growth and proliferation (see, e.g., refs. 1-6).Rat ventral prostate is a male accessory sex gland whose growth and functions are strictly dependent on androgens whose actions are largely mediated through regulation of transcriptional activity (7-10). We have employed androgen action on rat ventral prostate as an experimental model in our studies on the relation of CK-2 to growth control and have shown that phosph...

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