title: Role of the chromobox protein CBX7 in lymphomagenesis.
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.
authors: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
authors: Clare L
authors: CL
authors: Scott
authors: Jésus
authors: J
authors: Gil
authors: Eva
authors: E
authors: Hernando
authors: Julie
authors: J
authors: Teruya-Feldstein
authors: Masako
authors: M
authors: Narita
authors: Dolores
authors: D
authors: Martínez
authors: Tapio
authors: T
authors: Visakorpi
authors: David
authors: D
authors: Mu
authors: Carlos
authors: C
authors: Cordon-Cardo
authors: Gordon
authors: G
authors: Peters
authors: David
authors: D
authors: Beach
authors: Scott W
authors: SW
authors: Lowe
mesh_terms: 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
chemical_list: 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