title: c-Myc and E2F1 drive PBK/TOPK expression in high-grade malignant lymphomas.
abstract: c-Myc has been implicated in a variety of hematologic malignancies including Burkitt's lymphoma. Targeting c-Myc driven growth pathways could be therapeutically useful but might require the identification of critical downstream proteins. Here we show that the serine-threonine kinase PBK/TOPK is frequently overexpressed in high-grade lymphomas and its expression is positively correlated to that of c-Myc and E2F1. Further we demonstrate that c-Myc regulates PBK expression through E2F1. Additionally, inhibition of c-Myc, E2F1 or PBK comparably decreased cell growth and survival. In conclusion, a c-Myc-E2F1-PBK signaling pathway operates in high-grade lymphomas and may provide a useful target for novel antineoplastic therapeutics.
authors.affiliation: Marlene and Stewart Greenebaum Cancer Center and Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Gartenhaus
authors.forename: Xianfeng F
authors.initials: XF
authors.lastname: Zhao
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Fang
authors.forename: Samuel
authors.initials: S
authors.lastname: Minkove
authors.forename: Daniella E
authors.initials: DE
authors.lastname: Poss
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Rapoport
mesh_terms: D050687:E2F1 Transcription Factor / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000378:metabolism* / Q000473:pathology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D046888:Tissue Array Analysis
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase