Differential regulation of WNT2 and WNT2B expression in human cancer.

WNT2 is one of proto-oncogenes to activate the beta-catenin - TCF signaling pathway. WNT2B is a paralogue of WNT2, which encodes WNT2B1 and WNT2B2 isoforms due to alternative splicing using alternative promoter. Here, regulation of WNT2, WNT2B1, and WNT2B2 mRNAs in MCF-7 cells (breast cancer), NT2 cells (teratocarcinoma), and MKN45 cells (gastric cancer) were investigated. WNT2B2, but not WNT2 and WNT2B1, was expressed in MCF-7 cells. beta-estradiol (100 nM) induced a transient up-regulation of WNT2 in MCF-7 cells, and also induced down-regulation of WNT2B2. WNT2B2, but not WNT2B1, was expressed in NT2 cells, and WNT2 was slightly expressed in NT2 cells. Retinoic acid (10 microM) induced a transient up-regulation of WNT2 in NT2 cells. WNT2B2, but not WNT2 and WNT2B1, was slightly expressed MKN45 cells, and tumor necrosis factor alpha did not affect expression of WNT2, WNT2B1, and WNT2B2 mRNAs in MKN45 cells. This is the first report on differential regulation of WNT2, WNT2B1, and WNT2B2 mRNAs in human cancer cell lines. Up-regulation of WNT2 mRNA by estrogen might play a key role in some cases of human breast cancer through activation of the beta-catenin - TCF signaling pathway.