Beta-catenin/Tcf-1-mediated Transactivation of Cyclin D1 Promoter Is Negatively Regulated by Thyroid Hormone

Biochem Biophys Res Commun. 2003 Sep 19;309(2):408-13. doi: 10.1016/j.bbrc.2003.08.019.

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