Role of protein kinase CK2 in the regulation of tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis in prostate cancer cells.
Protein kinase CK2 (formerly casein kinase 2 or II) is a ubiquitous and highly conserved protein Ser/Thr kinase that plays diverse roles such as in cell proliferation and apoptosis. With respect to the latter, we originally showed that elevated CK2 could suppress various types of apoptosis in prostate cancer cells; however, the downstream pathways that respond to CK2 for mediating the suppression of apoptosis have not been fully elucidated. Here, we report studies on the role of CK2 in influencing activities associated with tumor necrosis factor-related ligand (TRAIL/Apo2-L)-mediated apoptosis in prostate carcinoma cells. To that end, we show that both androgen-insensitive (PC-3) and androgen-sensitive (ALVA-41) prostate cancer cells are sensitized to TRAIL by chemical inhibition of CK2 using its specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB). Furthermore, we have shown that overexpression of CK2alpha using pcDNA6-CK2alpha protected prostatic cancer cells from TRAIL-mediated apoptosis by affecting various activities associated with this process. Thus, overexpression of CK2 resulted in the suppression of TRAIL-induced apoptosis via its effects on the activation of caspases, DNA fragmentation, and downstream cleavage of lamin A. In addition, the overexpression of CK2 blocked the mitochondrial apoptosis machinery engaged by TRAIL. These findings define the important role of CK2 in TRAIL signaling in androgen-sensitive and -insensitive prostatic carcinoma cells. Our data support the potential usefulness of anticancer strategies that may involve the combination of TRAIL and down-regulation of CK2.
Wang
Guixia
G
Cellular and Molecular Biochemistry Research Laboratory, Minneapolis Veterans Affairs Medical Center, Minneapolis, Minnesota 55417, USA.
Ahmad
Kashif A
KA
Ahmed
Khalil
K
D000728:Androgens / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000494:pharmacology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D034904:Lamin Type A / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
C405354:4,5,6,7-tetrabromobenzotriazole; D000728:Androgens; D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; D034904:Lamin Type A; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D047390:Casein Kinase II