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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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.
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