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.
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
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
Nature
Date: Apr. 14, 2005
PubMed ID: 15829968
View in: Pubmed Google Scholar
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