Role of the chromobox protein CBX7 in lymphomagenesis.
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.
Scott
Clare L
CL
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Gil
Jésus
J
Hernando
Eva
E
Teruya-Feldstein
Julie
J
Narita
Masako
M
Martínez
Dolores
D
Visakorpi
Tapio
T
Mu
David
D
Cordon-Cardo
Carlos
C
Peters
Gordon
G
Beach
David
D
Lowe
Scott W
SW
D000818:Animals; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
C503627:CBX7 protein, human; C519505:Cbx7 protein, mouse; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D063150:Polycomb Repressive Complex 1