부산대학교 도서관

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 TRβ1 and wild-type or mutant β-catenin (SA) into 293T cells. In the presence of T3, β-catenin-dependent transactivation of cyclin D1 promoter was suppressed by co-transfection of TRβ1. The suppression by T3/TRβ1 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/TRβ1. Furthermore, inhibition of endogenous wild-type β-catenin by T3/TRβ1 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. [Copyright &y& Elsevier]