Protein kinase CK2 (formerly casein kinase II) is a serine/threonine kinase
overexpressed in many human tumors, transformed cell lines, and rapidly pr
oliferating tissues. Recent data have shown that many cancers involve inapp
ropriate reactivation of Wnt signaling through ectopic expression of Wnts t
hemselves, as has been seen in a number of human breast cancers, or through
mutation of intermediates in the Wnt pathway, such as adenomatous polyposi
s coli or beta-catenin, as described in colon and other cancers. Wnts are s
ecreted factors that are important in embryonic development, but overexpres
sion of certain Wnts, such as Wnt-1, leads to proliferation and transformat
ion of cells. We report that upon stable transfection of Wnt-1 into the mou
se mammary epithelial cell line C57MG, morphological changes and increased
proliferation are accompanied by increased levels of CK2, as well as of bet
a-catenin, CK2 and beta-catenin co-precipitate with the Dvl proteins, which
are Wnt signaling intermediates. A major phosphoprotein of the size of bet
a-catenin appears in in vitro kinase reactions performed on the Dvl immunop
recipitates. In vitro translated beta-catenin, Dvl-2, and Dvl-3 are phospho
rylated by CK2. The selective CK2 inhibitor apigenin blocks proliferation o
f Wnt-1-transfected cells, abrogates phosphorylation of beta-catenin, and r
educes beta-catenin and Dvl protein levels. These results demonstrate that
endogenous CK2 is a positive regulator of Wnt signaling and growth of mamma
ry epithelial cells.