Protein kinase CKII (i.e. casein kinase 11, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e. g. colorectal carcinomas) when compared to the corresponding nonneoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular extracts from solid tumours followed by immunostaining with an anti-CKII polyclonal antibody, (b) immunohistochemical staining of cells from tissue sections and (c) by activity measurements using the CKII-specific synthetic peptide (RRRDDDSDDD). The maximum observed activity in the colorectal carcinomas investigated was up to eightfold higher in the tumour specimens than in the non-neoplastic tissue (i.e. colorectal mucosa). The activity range was between 33 -350 U/ mg protein and in the case of colorectal mucosa 13 -106 U/mg protein. The amount of CKII determined in the individual tumours was in the range 0.4-1.6 nmol/g tissue.Casein kinase I1 (CKII) is found in the cytoplasm and in the nucleus. The latter form has also been called NII, although biochemical and biophysical data suggest that it is the same enzyme. The name is misleading inasmuch as the name casein kinase I1 was coined according to its test substrate which is casein.CKII is a ubiquitous protein kinase which is widely distributed in different eukaryotic cell types [I]. The level of enzyme activity has been shown to be elevated in transformed cells [2], in mitogen-stimulated lymphocytes [3], during mouse embryogenesis [4], during differentiation of 3T3-LI cells [5] and during progesterone-induced maturation of oocytes [6]. All these findings suggest a functional role for CKII in the regulation of cellular growth. In detail, CKII has been thought to play a role in the regulation of protein synthesis 141. By immunohistochemical studies, CKII was shown to be highly concentrated in the nucleolus [15, 161, i.e. in the same cellular compartment where some of its potential physiological substrates (RNA polymerase I, topoisomerases I and 11, and nucleolin) are located. These nucleolar proteins are involved in the first steps of cellular growth and CKII seems to be the key enzyme controlling the very first steps of proliferation at the level of rRNA synthesis. Here we demonstrate that CKII is elevated in human solid tumours when compared to nonneoplastic tissue of the same patient. The results are supported by immunohistochemical studies. In addition, we have shown that CKII is not exclusively elevated in tumour cells but also in normal tissue with high mitotic activity (e. g. colorectal mucosa).Thus the data presented are in good agreement with earlier studies, where elevated CKII activity was detected in tumour cell lines [2] and also in non-neoplastic tissue (e.g. during certain stages of embryogenesis) [4]. A comparison with the proliferation marker Ki67 [I71 also suggests that there may be a potential application for CKII as a marker protein for proliferation. MATERIALS AND METHODS Breast carcinomasA tumour and non-neoplastic tissue from a patient with an i...

Mouse embryos at various stages of development were used to study the relationship of protein kinase activities with normal embryogenesis. Casein kinase I1 (CKII) activity in developing mouse embryos shows a 3 -4fold activity increase at day 12 of gestation. Together with the CKII activity, increased phosphorylation of a 110-kDa protein is observed. Treatment of the embryo extracts with heparin, a highly specific inhibitor of CKII activity, results in a drastic reduction of the 110-kDa protein phosphorylation indicating that the protein might be a CKIIspecific substrate. Rapidly proliferating mouse tumour cells also show an enhanced CKII activity. Here too, a 110-kDa phosphoprotein was the major phosphoryl acceptor. Partial proteolytic digestion shows that both proteins are identical. Other protein kinases tested (CAMP-and cGMP-dependent protein kinases) only show a basal level of enzyme activity with minor alterations throughout the different stages of embryogenesis investigated.Casein kinase I1 activity in established and experimentally transformed tumour cells has been shown to be enhanced at least 3 -5-fold compared to normal fibroblasts and primary tumour cell cultures [l]. In contrast, other protein kinases, e. g. CAMP-and cGMP-dependent protein kinases, did not show elevated activities. Casein kinase I1 is a well characterized protein kinase which has unique properties such as using ATP as well as GTP as phosphoryl donors. Furthermore this enzyme has been found in almost all eukaryotic organisms so far investigated [2]. Phosphorylation of key proteins of transcription and translation (e. g. topoisomerase I1[3], RNA polymerases I and I1 [4, 51, translational initiation factor eIF-3 [6] and proteins of the RNP particles [7]) from CKII have been shown to occur in vivo and in vitro. However, little information exists concerning the role of this enzyme during normal cell life. The elevated CKII activities observed in rapidly proliferating tumour cell lines led us to search for stages during normal development of an organism where naturally high proliferation rates prevail. This is the case during fetal and embryonic development. There are stages during mouse embryogenesis where the proliferation rate increases 10-fold within 24 h. Since phosphorylation of nuclear proteins (e. g. RNA polymerases I and I1 and topoisomerase 11) has generally been regarded as a means of modulating gene transcription [8, 91, it is feasible to assume that enzymes

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