Regulation of cyclooxygenase-2 and periostin by Wnt-3 in mouse mammary epithelial cells

Wnt family members are critical in developmental processes and have been sh own to promote carcinogenesis when ectopically expressed in the mouse mamma ry gland. The gene expression pattern mediated by Wnt is pivotal for these diverse responses. The Wnt pathway has been conserved among different speci es. Genetic studies have shown that Wnt effects are mediated, at least in p art, by beta-catenin, which regulates transcription of "downstream genes." Wnt stimulation inactivates glycogen-synthase kinase-3 beta (GSK-8) with su bsequent stabilization of beta-catenin, which after heterodimerizing with l ymphocyte enhancer factor-YT-cell factor cofactors stimulates transcription . To establish whether Wnt-stimulated transcription is mediated solely by b eta-catenin, a comparison was made of gene expression profiles in response to Wnt-3, overexpression of beta-catenin, and inhibition of GSK-3. Infectio n of cells with Wnt-3 and inhibition of GSK-3 regulate a set of genes that include cyclooxygenase-2 and periostin. Interestingly, overexpression of be ta-catenin or reducing beta-catenin levels with antisense oligonucleotide t ransfection did not have any effect on cyclooxygenase-2 or periostin expres sion, thereby defining a Wnt pathway, which cannot be mimicked by beta-cate nin overexpression.