Frizzled (FZD) genes encode receptors for WNTs, which play key roles in carcinogenesis and embryogenesis. We have previously cloned the FZD10 gene, and demonstrated up-regulation of FZD10 mRNA in the cervical cancer cell line HeLa S3, gastric cancer cell lines TMK1 and MKN74, and 4 cases out of 10 cases of primary gastric cancer. Here, effects of β-estradiol, retinoic acid, and inflammatory cytokines on expression of FZD10 mRNA in human cancer cell lines were investigated. FZD10 mRNA was undetectable in MCF-7 cells derived from breast cancer, and was significantly up-regulated by β-estradiol in MCF-7 cells with a peak at 24 h after treatment. FZD10 mRNA was expressed in NT2 cells, which are reported to differentiate into neuronal cells after exposure to retinoic acid. Although expression level of FZD10 mRNA was unchanged until 36 h after retinoic-acid treatment, FZD10 mRNA was up-regulated at 48 and 72 h after retinoic-acid treatment in NT2 cells. Effects of inflammatory cytokines on FZD10 mRNA expression in a gastric cancer cell line MKN45 was next investigated. FZD10 mRNA was undetectable in MKN45 cells, and was not up-regulated by IFNγ and TNFα in MKN45 cells. Because we have previously demonstrated up-regulation of WNT2 mRNA by β-estradiol in MCF-7 cells, FZD10 and WNT2 mRNAs were found to be up-regulated together by β-estradiol in MCF-7 cells with the same time course. Synchronous up-regulation of FZD10 and WNT2 mRNAs might lead to activation of the WNT signaling pathway in human breast cancer.

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