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Nuclear Matrix Targeting of the Protein Kinase CK2 Signal as a Common Downstream Response to Androgen or Growth Factor Stimulation of Prostate Cancer Cells¹

Cellular and Molecular Biochemistry Research Laboratory (151), Department of Laboratory Medicine and Pathology, University of Minnesota, and the Department of Veterans Affairs Medical Center, Minneapolis, Minnesota 55417

Protein kinase CK2, a messenger-independent serine/threonine kinase, has been implicated in cell growth. Androgenic stimulus in rat prostate modulates its association with nuclear matrix (NM) and chromatin. Because the growth of human prostate carcinoma cells is influenced by androgens and/or growth factors, we determined the nature of CK2 signaling in the NM in response to androgen and growth factor stimuli. Androgen-sensitive LNCaP and androgen-insensitive PC-3 cells were cultured in media to regulate their growth in the presence of 5-dihydrotestosterone (5-DHT) or growth factors (epidermal growth factor, keratinocyte growth factor, and transforming growth factor ). The activity of CK2 was measured in the cytosolic and NM fractions isolated from these cells after treatment with growth stimuli. The changes in CK2 in various fractions were also confirmed by immunoblotting with a specific antibody. LNCaP cells responded to both 5-DHT and growth factors for growth. The presence of these agents in the culture medium evoked a translocation of CK2 to the NM from the cytosol. The PC-3 cells did not respond to 5-DHT for growth but did respond to growth factors. Under these conditions, there was also a translocation of CK2 to the NM concomitant with a decrease in the cytosolic fraction. These results suggest that CK2 translocation to the NM occurs in response to various growth stimuli in cells in culture. Thus, CK2 is a common downstream signal transducer in response to diverse growth stimuli that may relate to the pathobiology of prostate cancer cells.

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