The role of NF-κB-1 and NF-κB-2-mediated resistance to apoptosis in lymphomas

Bernal‐Mizrachi, Leon; Lovly, Christine M.; Ratner, Lee

doi:10.1073/pnas.0507809103

Cited by 102 publications

(90 citation statements)

References 47 publications

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“…Moreover, two B-lymphoma-like cell lines with high NF-B activity (IB4, due to expression of the LMP1 protein of EBV (41), and RC-K8, due to inactivating mutations in IB␣ (25)) express little to no CD10 protein (Fig. 1A), whereas four B-lymphoma cell lines not known to have high NF-B activity (BJAB (21), SUDHL-4 (23), BL-41 (14), Daudi (25,45,46)) have high CD10 levels.…”

Section: Discussionmentioning

confidence: 99%

NF-κB Down-regulates Expression of the B-lymphoma Marker CD10 through a miR-155/PU.1 Pathway

Thompson¹,

Herscovitch²,

Zhao

et al. 2011

Journal of Biological Chemistry

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The NF-B signaling pathway is misregulated in a variety of human diseases including many chronic inflammatory diseases and cancers. As such, an understanding of the molecular details of NF-B-dependent gene networks has implications for improved disease diagnoses and therapies. CD10, also known as the common acute lymphocytic leukemia antigen (CALLA) or neutral endopeptidase, is a cellsurface zinc metalloendopeptidase (1, 2). The ability of CD10 to cleave signal peptides at the cell surface can affect cell proliferation, differentiation, and migration (2-4). Expression of CD10 can be used as a diagnostic marker for a variety of cancers (5-9). Relevant to this study, CD10 is highly expressed in the germinal center B-cell (GCB) 6 molecular subtype of diffuse large B-cell lymphoma (DLBCL), whereas CD10 expression is low in the activated B-cell (ABC) subtype of DLBCL (8, 9). ABC DLBCLs also have a high NF-B gene expression profile and a poorer clinical prognosis as compared with GCB DLBCLs (10). As such, reduced expression of CD10 and high NF-B activity are both correlated with a less favorable DLBCL patient outcome (10 -12).The correlation between high NF-B activity and reduced CD10 expression has been observed in several other settings as well. We previously showed that overexpression of an activated mutant of the NF-B family transcription factor REL in the GCB-like B-lymphoma cell line BJAB leads to reduced expression of CD10 (13). Infection of cells with Epstein-Barr virus (EBV) or human cytomegalovirus, both inducers of NF-B, causes reduced expression of CD10 (14, 15). Taken together, such results suggested to us that NF-B or a target of NF-B is involved in repressing CD10 gene/protein expression in certain B-cell lymphomas.Little is known about the control of CD10 transcription. Sequence analysis of the CD10 promoter/enhancer region revealed the presence of three consensus binding sites for transcription factor PU.1 (16). PU.1 is a member of the Ets family of transcription factors and is required for proper Bcell development and differentiation (17). Additionally, increased PU.1 expression has been correlated with the GCB subtype of DLBCL (8). Therefore, we were interested in investigating whether PU.1 contributes to the regulation of CD10 expression in B-cell lymphoma.In this report, we provide evidence for a functional link between activation of NF-B and reduced expression of CD10. We show that activation of NF-B in the GCB-like DLBCL cell line BJAB leads to reduced CD10 expression. Our data are consistent with a pathway in which NF-B-induced up-regulation of micro-RNA miR-155 leads to down-regulation of PU.1 protein levels, and consequently, reduced levels of * This work was supported, in whole or in part, by National Institutes of Health Grant CA047763 and American Recovery and Reinvestment Act of 2009 supplement Grant CA047763021S3 (to T. D. G.). □ S The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1 and Fig. S1

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Section: Discussionmentioning

confidence: 99%

NF-κB Down-regulates Expression of the B-lymphoma Marker CD10 through a miR-155/PU.1 Pathway

Thompson¹,

Herscovitch²,

Zhao

et al. 2011

Journal of Biological Chemistry

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“…37 It has been reported that the classical and alternative NF-B pathways differentially control genes with anti-apoptotic functions in lymphoma cell lines. 50 In transformation by Tax, it has been reported that the alternative pathway is critical. 51 This study demonstrates the selective suppression of the classical NF-B pathway by HBZ, a phenomenon that selectively modulates NF-B activation by Tax.…”

Section: Discussionmentioning

confidence: 99%

Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-κB

Zhao

Yasunaga

Satou

et al. 2009

Blood

157

186

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“…These agents may exert their chemo-sensitizing effect via regulation of NF-κB pathway. 49 It is believed that AA +/-DAS treatment may inactivate NF-κB, thus contributes to growth inhibition and apoptosis, since NF-κB-induced apoptosis resistance has been implicated in chemotherapeutic failures in cancer treatment. 50 AA +/-DAS significantly inhibited Bcl2 gene joined with activated Bax gene.…”

Section: Discussionmentioning

confidence: 99%

Vitamin C and diallyl sulfide as chemosensitizers to cisplatin in treating hepatocellular carcinoma

Abdel-Hamid¹,

Nazmy²,

Nazmy³

2011

JST

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BackgroundThe resistance to chemotherapy is a major obstacle in the treatment of hepatocellular carcinoma (HCC), necessitating the discovery of additional agents. The use of natural products in this respect is extensively under investigation. Methods Two hundred and ten male albino rats were used, divided into 14 groups. Selected groups were pre-treated with vitamin C (ascorbic acid, AA) and/or diallyl sulphide (DAS). Hepatocellular dysplasia was initiated by a single intra-peritoneal (IP) injection of diethyl nitrosamine (DENA), diabetes was induced by a single IP injection of Streptozotocin (STZ). Other groups were treated with cisplatin (CP) alone or combined with AA and/or DAS for 14 weeks. This work aims to check if naturally occurring materials can help in improving response to CP chemotherapy using ploylol profile as a new index in management of HCC. ResultsThe results revealed that DENA significantly increased relative liver weight, serum ALT, AST and GGT activities, AFP, TNF-α and IL-6 levels, expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and Bcl2 proteins in the liver with decrease in body weight, expression of Bax protein and Bax/Bcl2 ratio in the liver. These effects were more pronounced in DENA+STZ group. These parameters showed relative correlation to AFP levels in HCC, in response to AA and/or DAS treatment except for SDH. Treatment with CP and/or AA and/or DAS significantly modulated most of these parameters except for SDH which showed no significant change in response to the suggested treatment. ConclusionsIn conclusion, AA and/or DAS showed apparent chemo-sensitizing, anti-inflammatory, AR inhibitory, apoptotic inducing and anti-diabetic activities, indicating new aspects for use as adjuvant to chemotherapy. Induction of diabetes in hepatocellular dysplasia -bearing rats showed higher resistance to chemotherapy. Ploylol profile is a useful prognostic tool in HCC patients with diabetic interference.

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The role of NF-κB-1 and NF-κB-2-mediated resistance to apoptosis in lymphomas

Cited by 102 publications

References 47 publications

NF-κB Down-regulates Expression of the B-lymphoma Marker CD10 through a miR-155/PU.1 Pathway

NF-κB Down-regulates Expression of the B-lymphoma Marker CD10 through a miR-155/PU.1 Pathway

Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-κB

Vitamin C and diallyl sulfide as chemosensitizers to cisplatin in treating hepatocellular carcinoma

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