title: Protein kinase CK2 promotes cancer cell viability via up-regulation of cyclooxygenase-2 expression and enhanced prostaglandin E2 production.
abstract: Augmented expression of protein kinase CK2 is associated with hyperproliferation and resistance to apoptosis in cancer cells. Effects of CK2 are at least partially linked to signaling via the Wnt/β-catenin pathway, which is dramatically enhanced in colon cancer. Cyclooxygenase-2 (COX-2), a Wnt/β-catenin target gene, has been associated with enhanced cancer progression and metastasis. However, the possibility that a connection may exist between CK2 and COX-2 has not been explored previously. Here we investigated changes in COX-2 expression and activity upon CK2 modulation and evaluated how these changes affected cell viability. COX-2 expression and cell viability decreased upon selective inhibition of COX-2 with SC-791 or CK2 with 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT), both in human colon (HT29-ATCC, HT29-US, DLD-1) and breast (ZR-75) cancer cells, as well as in human embryonic kidney (HEK-293T) cells. On the other hand, ectopic CK2α expression promoted up-regulation of COX-2 by activating the Wnt/β-catenin pathway in HEK-293T cells. Noteworthy, over-expression of either CK2α, β-catenin or COX-2, as well as supplementation of the medium with prostaglandin E2 (PGE2), all were individually sufficient to overcome limitations in cell viability triggered by CK2 inhibition either upon addition of DMAT or over-expression of a dominant negative CK2α variant. Altogether, these findings provide new insight to the role of CK2 in cancer by up-regulating COX-2 expression and thereby PGE2 production.
authors: Institute of Biomedical Sciences (ICBM), Faculty of Medicine, University of Chile, Santiago, Chile.
authors: Roger
authors: R
authors: Yefi
authors: Daniela P
authors: DP
authors: Ponce
authors: Ignacio
authors: I
authors: Niechi
authors: Eduardo
authors: E
authors: Silva
authors: Pablo
authors: P
authors: Cabello
authors: Diego A
authors: DA
authors: Rodriguez
authors: Katherine
authors: K
authors: Marcelain
authors: Ricardo
authors: R
authors: Armisen
authors: Andrew F G
authors: AF
authors: Quest
authors: Julio C
authors: JC
authors: Tapia
mesh_terms: D017209:Apoptosis; D047390:Casein Kinase II / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D015854:Up-Regulation / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051176:beta Catenin; D051546:Cyclooxygenase 2; D047390:Casein Kinase II; D015232:Dinoprostone