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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Beta-catenin/Tcf-1- mediated transactivation of cyclin D1 promoter is negatively regulated by thyroid hormone.

Cyclin D1 is an oncogenic cyclin frequently over-expressed in cancer. To examine the effect of thyroid hormone (T3) and its receptor (TR) on the transcription of cyclin D1 gene, we co-transfected the chloramphenicol acetyl-transferase (CAT) reporter plasmid containing cyclin D1 promoter together with the expression plasmids for TRbeta1 and wild-type or mutant beta-catenin (SA) into 293T cells. In the presence of T3, beta-catenin-dependent transactivation of cyclin D1 promoter was suppressed by co-transfection of TRbeta1. The suppression by T3/TRbeta1 was in a dose-dependent manner. The CAT reporter gene in which Tcf/Lef-1 sites were fused to heterologous promoter was also suppressed by T3/TRbeta1. Furthermore, inhibition of endogenous wild-type beta-catenin by T3/TRbeta1 was observed in SW480 colon carcinoma cells with mutation of the adenomatous polyposis coli gene. These results indicate that the T3-bound TR inhibits the transcription of cyclin D1 through the Tcf/Lef-1 site, which is positively regulated by the Wnt-signaling pathway.[1]


  1. Beta-catenin/Tcf-1-mediated transactivation of cyclin D1 promoter is negatively regulated by thyroid hormone. Natsume, H., Sasaki, S., Kitagawa, M., Kashiwabara, Y., Matsushita, A., Nakano, K., Nishiyama, K., Nagayama, K., Misawa, H., Masuda, H., Nakamura, H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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