Role of the chromobox protein CBX7 in lymphomagenesis
- Author(s)
- Scott, CL; Gil, J; Hernando, E; Teruya-Feldstein, J; Narita, M; Martinez, D; Visakorpi, T; Mu, D; Cordon-Cardo, C; Peters, G; Beach, D; Lowe, SW;
- Details
- Publication Year 2007-03-27,Volume 104,Issue #13,Page 5389-5394
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- 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.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- MYC TRANSGENIC MICE; LARGE-CELL LYMPHOMA; FOLLICULAR LYMPHOMA; C-MYC; INK4A LOCUS; B-CELL; TRANSFORMATION; BMI-1; CANCER; EXPRESSION
- Publisher's Version
- https://doi.org/10.1073/pnas.0608721104
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2007-03-27 12:00:00