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Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes.

Defining the molecular strategies that integrate diverse signalling pathways in the expression of specific gene programmes that are critical in homeostasis and disease remains a central issue in biology. This is particularly pertinent in cancer biology because downregulation of tumour metastasis suppressor genes is a common occurrence, and the underlying molecular mechanisms are not well established. Here we report that the downregulation of a metastasis suppressor gene, KAI1, in prostate cancer cells involves the inhibitory actions of beta-catenin, along with a reptin chromatin remodelling complex. This inhibitory function of beta-catenin-reptin requires both increased beta-catenin expression and recruitment of histone deacetylase activity. The coordinated actions of beta-catenin-reptin components that mediate the repressive state serve to antagonize a Tip60 coactivator complex that is required for activation; the balance of these opposing complexes controls the expression of KAI1 and metastatic potential. The molecular mechanisms underlying the antagonistic regulation of beta-catenin-reptin and the Tip60 coactivator complexes for the metastasis suppressor gene, KAI1, are likely to be prototypic of a selective downregulation strategy for many genes, including a subset of NF-kappaB target genes.

Pubmed ID: 15829968


  • Kim JH
  • Kim B
  • Cai L
  • Choi HJ
  • Ohgi KA
  • Tran C
  • Chen C
  • Chung CH
  • Huber O
  • Rose DW
  • Sawyers CL
  • Rosenfeld MG
  • Baek SH



Publication Data

April 14, 2005

Associated Grants


Mesh Terms

  • Acetyltransferases
  • Animals
  • Antigens, CD
  • Antigens, CD82
  • Cell Line, Tumor
  • Chromatin Assembly and Disassembly
  • Collagen
  • Cytoskeletal Proteins
  • Down-Regulation
  • Drug Combinations
  • Gene Expression Regulation, Neoplastic
  • Histone Acetyltransferases
  • Humans
  • Laminin
  • Male
  • Membrane Glycoproteins
  • Mice
  • NF-kappa B
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Promoter Regions, Genetic
  • Prostatic Neoplasms
  • Proteoglycans
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Trans-Activators
  • Transcription, Genetic
  • beta Catenin