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Emerging roles of Polycomb silencing in X-inactivation and stem cell maintenance.

Muyrers-Chen, I; Hernández-Muñoz, I; Lund, A H; Valk-Lingbeek, M E; van der Stoop, P; Boutsma, E; Tolhuis, B; Bruggeman, S W M; Taghavi, P; Verhoeven, E; Hulsman, D; Noback, S; Tanger, E; Theunissen, H; van Lohuizen, M.

Cold Spring Harb Symp Quant Biol ; 69: 319-26, 2004.

Article in English | MEDLINE | ID: mdl-16117664

Subject(s)

Dosage Compensation, Genetic , Drosophila Proteins/genetics , Gene Silencing , Stem Cells/metabolism , Animals , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Drosophila/genetics , Drosophila/metabolism , Drosophila Proteins/metabolism , Epigenesis, Genetic , Female , Histone-Lysine N-Methyltransferase , Histones/chemistry , Histones/metabolism , Humans , Male , Models, Genetic , Myeloid-Lymphoid Leukemia Protein , Neoplasms/etiology , Nucleosomes/metabolism , Polycomb Repressive Complex 1 , Polycomb-Group Proteins , Proto-Oncogenes/genetics , Repressor Proteins/genetics , Repressor Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Ubiquitin/metabolism

Senescence bypass screen identifies TBX2, which represses Cdkn2a (p19(ARF)) and is amplified in a subset of human breast cancers.

Jacobs, J J; Keblusek, P; Robanus-Maandag, E; Kristel, P; Lingbeek, M; Nederlof, P M; van Welsem, T; van de Vijver, M J; Koh, E Y; Daley, G Q; van Lohuizen, M.

Nat Genet ; 26(3): 291-9, 2000 Nov.

Article in English | MEDLINE | ID: mdl-11062467

ABSTRACT

To identify new immortalizing genes with potential roles in tumorigenesis, we performed a genetic screen aimed to bypass the rapid and tight senescence arrest of primary fibroblasts deficient for the oncogene Bmi1. We identified the T-box member TBX2 as a potent immortalizing gene that acts by downregulating Cdkn2a (p19(ARF)). TBX2 represses the Cdkn2a (p19(ARF)) promoter and attenuates E2F1, Myc or HRAS-mediated induction of Cdkn2a (p19(ARF)). We found TBX2 to be amplified in a subset of primary human breast cancers, indicating that it might contribute to breast cancer development.

Subject(s)

Adenocarcinoma/genetics , Breast Neoplasms/genetics , Cell Cycle Proteins/physiology , Cellular Senescence/genetics , Chromosomes, Human, Pair 17/genetics , DNA-Binding Proteins , Gene Amplification , Gene Expression Regulation, Neoplastic , Neoplasm Proteins/physiology , Protein Biosynthesis , Repressor Proteins/physiology , T-Box Domain Proteins/physiology , Adenocarcinoma/metabolism , Animals , Breast Neoplasms/metabolism , COS Cells , Carrier Proteins/genetics , Cell Cycle Proteins/genetics , Cell Cycle Proteins/isolation & purification , Cell Transformation, Neoplastic/genetics , Cells, Cultured , Cyclin-Dependent Kinase Inhibitor p16 , E2F Transcription Factors , E2F1 Transcription Factor , Female , Fibroblasts/cytology , Fibroblasts/metabolism , Gene Deletion , Genes, BRCA1 , Humans , Mice , Neoplasm Proteins/biosynthesis , Neoplasm Proteins/genetics , Neoplasm Proteins/isolation & purification , Neoplastic Syndromes, Hereditary/genetics , Nuclear Proteins/genetics , Oncogenes , Polycomb Repressive Complex 1 , Promoter Regions, Genetic , Proteins/genetics , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-myc/antagonists & inhibitors , Proto-Oncogene Proteins p21(ras)/antagonists & inhibitors , Repressor Proteins/genetics , Repressor Proteins/isolation & purification , Retinoblastoma-Binding Protein 1 , T-Box Domain Proteins/genetics , T-Box Domain Proteins/isolation & purification , Transcription Factor DP1 , Transcription Factors/antagonists & inhibitors , Transfection , Tumor Cells, Cultured , Tumor Suppressor Protein p14ARF

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