Abstract
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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cells, Cultured
-
Colonic Neoplasms / genetics*
-
Colonic Neoplasms / metabolism*
-
Cyclin D1 / genetics*
-
Cyclin D1 / metabolism*
-
Cytoskeletal Proteins / genetics
-
Cytoskeletal Proteins / metabolism
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / metabolism
-
Dose-Response Relationship, Drug
-
Gene Expression Regulation / drug effects
-
Genes, bcl-1 / drug effects
-
Humans
-
Kidney / embryology
-
Kidney / metabolism*
-
Lymphoid Enhancer-Binding Factor 1
-
Promoter Regions, Genetic / drug effects
-
Receptors, Thyroid Hormone / metabolism
-
Trans-Activators / genetics
-
Trans-Activators / metabolism
-
Transcription Factors / genetics
-
Transcription Factors / metabolism
-
Transcriptional Activation / drug effects*
-
Transfection
-
Triiodothyronine / pharmacology*
-
Tumor Cells, Cultured / drug effects
-
Tumor Cells, Cultured / metabolism
-
beta Catenin
Substances
-
CTNNB1 protein, human
-
Cytoskeletal Proteins
-
DNA-Binding Proteins
-
Lymphoid Enhancer-Binding Factor 1
-
Receptors, Thyroid Hormone
-
Trans-Activators
-
Transcription Factors
-
beta Catenin
-
Triiodothyronine
-
Cyclin D1