TY - JOUR
T1 - Bmi-1 is induced by the Epstein-Barr virus oncogene LMP1 and regulates the expression of viral target genes in Hodgkin lymphoma cells
AU - Dutton, Amanda
AU - Woodman, Ciaran B.
AU - Chukwuma, Marilyn B.
AU - Last, James I.K.
AU - Wei, Wenbin
AU - Vockerodt, Martina
AU - Baumforth, Karl R.N.
AU - Flavell, Joanne R.
AU - Rowe, Martin
AU - Taylor, A. Malcolm R.
AU - Young, Lawrence S.
AU - Murray, Paul G.
PY - 2007/3/15
Y1 - 2007/3/15
N2 - Polycomb group (PcG) proteins are chromatin modifiers that are necessary for the maintenance and renewal of embryonic and adult stem cells. However, overexpression of the PcG protein, Bmi-1, causes lymphoma in transgenic mice. We show that Bmi-1 is up-regulated in Hodgkin lymphoma (HL) cells by the Epstein-Barr virus (EBV) oncogene latent membrane protein-1 (LMP1) and that this up-regulation is mediated by NF-κB signaling. We also show that Bmi-1 is up-regulated by NF-κB in EBV-negative HL cells. Down-regulation of LMP1 and Bmi-1 decreased the survival of HL cells, suggesting that Bmi-1 may mediate the prosurvival effects of LMP1-induced NF-κB signaling in HL cells. Transcriptional targets of Bmi-1 were identified after its knockdown in an HL cell line. We show here that Bmi-1 and LMP1 down-regulate the ataxia telangiectasia-mutated (ATM) tumor suppressor and conclude that Bmi-1 contributes to LMP1-induced oncogenesis in HL.
AB - Polycomb group (PcG) proteins are chromatin modifiers that are necessary for the maintenance and renewal of embryonic and adult stem cells. However, overexpression of the PcG protein, Bmi-1, causes lymphoma in transgenic mice. We show that Bmi-1 is up-regulated in Hodgkin lymphoma (HL) cells by the Epstein-Barr virus (EBV) oncogene latent membrane protein-1 (LMP1) and that this up-regulation is mediated by NF-κB signaling. We also show that Bmi-1 is up-regulated by NF-κB in EBV-negative HL cells. Down-regulation of LMP1 and Bmi-1 decreased the survival of HL cells, suggesting that Bmi-1 may mediate the prosurvival effects of LMP1-induced NF-κB signaling in HL cells. Transcriptional targets of Bmi-1 were identified after its knockdown in an HL cell line. We show here that Bmi-1 and LMP1 down-regulate the ataxia telangiectasia-mutated (ATM) tumor suppressor and conclude that Bmi-1 contributes to LMP1-induced oncogenesis in HL.
UR - http://www.scopus.com/inward/record.url?scp=33947262695&partnerID=8YFLogxK
U2 - 10.1182/blood-2006-05-020545
DO - 10.1182/blood-2006-05-020545
M3 - Article
C2 - 17148591
AN - SCOPUS:33947262695
SN - 0006-4971
VL - 109
SP - 2597
EP - 2603
JO - Blood
JF - Blood
IS - 6
ER -
