Expression and regulation of WNT8A and WNT8B mRNAs in human tumor cell lines: up-regulation of WNT8B mRNA by beta-estradiol in MCF-7 cells, and down-regulation of WNT8A and WNT8B mRNAs by retinoic acid in NT2 cells.

Xenopus wnt-8 (Xwnt-8) is one of the most potent Wnts to activate the WNT - beta-catenin - TCF signaling pathway. We have previously cloned and characterized WNT8A and WNT8B, two human homologues of Xwnt-8. Here, we investigated expression and regulation of WNT8A and WNT8B mRNAs in human tumor cell lines by using cDNA-PCR. WNT8A mRNA was undetectable in 7 pancreatic cancer cell lines, but WNT8B mRNA was detected in pancreatic cancer cell lines PSN-1, BxPC-3, MIA PaCa-2. Both WNT8A and WNT8B mRNAs were undetectable in 7 brain tumor cell lines. Although WNT8A mRNA was undetectable in 3 breast cancer cell lines, WNT8B mRNA was detected in the breast cancer cell line MCF-7. WNT8B mRNA, but not WNT8A mRNA, was significantly up-regulated by beta-estradiol in MCF-7 cells. WNT8A mRNA was detected in embryonal tumor cell lines NEC-14, NCC-IT, and NT2, while WNT8B mRNA was detected in embryonal tumor cell lines NEC-8, NEC-14, and NT2. Because NT2 cells differentiate into neuronal cells after all-trans retinoic-acid treatment, effects of all-trans retinoic acid on mRNA expression of WNT8A and WNT8B were next investigated. WNT8A and WNT8B mRNAs were down-regulated together in NT2 cells after all-trans retinoic-acid treatment. WNT8A and WNT8B might play key roles in embryonal tumors and embryonic stem cells through synergistic activation of the beta-catenin - TCF signaling pathway.