Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 13, Pages 5389-5394Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0608721104
Keywords
Ink4a-ARF; oncogene; polycomb; follicular lymphoma; p53
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Funding
- Medical Research Council [MC_U120085810] Funding Source: researchfish
- MRC [MC_U120085810] Funding Source: UKRI
- Medical Research Council [MC_U120085810] Funding Source: Medline
- NCI NIH HHS [P30 CA008748] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
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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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