Role of the chromobox protein CBX7 in lymphomagenesis

Scott, C. L., Gil, J., Hernando, E., Teruya-Feldstein, J., Narita, M., Martinez, D., Visakorpi, T., Mu, D., Cordon-Cardo, C., Peters, G., Beach, D., Lowe, S. W. (March 2007) Role of the chromobox protein CBX7 in lymphomagenesis. Proc Natl Acad Sci U S A, 104 (13). pp. 5389-94. ISSN 0027-8424 (Print)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/17374722
DOI: 10.1073/pnas.0608721104

Abstract

Chromobox 7 (CBX7) is a chromobox family protein and a component of the Polycomb repressive complex 1 (PRC1) that extends the lifespan of cultured epithelial cells and can act independently of BMI-1 to repress the INK4a/ARF tumor suppressor locus. To determine whether CBX7 might be oncogenic, we examined its expression pattern in a range of normal human tissues and tumor samples. CBX7 was expressed at high levels in germinal center lymphocytes and germinal center-derived follicular lymphomas, where elevated expression correlated with high c-Myc expression and a more advanced tumor grade. By targeting Cbx7 expression to the lymphoid compartment in mice, we showed that Cbx7 can initiate T cell lymphomagenesis and cooperate with c-Myc to produce highly aggressive B cell lymphomas. Furthermore, Cbx7 repressed transcription from the Ink4a/Arf locus and acted epistatically to the Arf-p53 pathway during tumorigenesis. These data identify CBX7 as a chromobox protein causally linked to cancer development and may help explain the low frequency of INK4a/ARF mutations observed in human follicular lymphoma.

Item Type: Paper
Uncontrolled Keywords: Animals Cyclin-Dependent Kinase Inhibitor p16/metabolism Epithelial Cells/cytology Humans Loss of Heterozygosity Lymphoma/ genetics/ metabolism Mice Mutation Neoplasms/metabolism Nuclear Proteins/ metabolism Proto-Oncogene Proteins c-myc/metabolism Repressor Proteins/chemistry/ metabolism/ physiology T-Lymphocytes/metabolism Tumor Suppressor Protein p53/metabolism
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
CSHL Authors:
Communities: CSHL labs > Lowe lab
Depositing User: Matt Covey
Date: 27 March 2007
Date Deposited: 28 Feb 2013 21:55
Last Modified: 09 Nov 2017 15:55
PMCID: PMC1828941
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27651

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