Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study

Lessard, Laurent; Lr, Bégin; Gleave, Martin; Mes-Masson, Anne-Marie; Saad, Fred

doi:10.1038/sj.bjc.6602796

Cited by 137 publications

(126 citation statements)

References 24 publications

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“…In primary prostate cancer patients, nuclear localization of RelB positively correlates to a patient's Gleason score [100], suggesting that non-canonical activation of RelB may play a significant pathological role in this cancer type. Interestingly, Xu et al [101] found that nuclear localiza-…”

Section: Additional Nf-κb Signaling By Genotoxic Agentsmentioning

confidence: 99%

Nuclear initiated NF-κB signaling: NEMO and ATM take center stage

2010

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A large body of literature describes elaborate NF-κB signaling networks induced by inflammatory and immune signals. Decades of research has revealed that transcriptionally functional NF-κB dimers are activated by two major pathways, canonical and non-canonical. Both pathways involve the release of NF-κB dimers from inactive cytoplasmic complexes to cause their nuclear translocation to modulate gene expression programs and biological responses. NF-κB is also responsive to genotoxic agents; however, signal communication networks that are initiated in the nucleus following DNA damage induction are less defined. Evidence in the literature supports the presence of such signaling pathways induced by multiple distinct genotoxic agents, resulting in the activation of cytoplasmic IKK complex. An example is a pathway that involves the DNA damage-responsive kinase ataxia telangiectasia mutated (ATM) and a series of post-translational modifications of NF-κB essential modulator (NEMO) in the nucleus of a genotoxinexposed cell. Recent evidence also suggests that this nuclear-initiated NF-κB signaling pathway plays significant physiological and pathological roles, particularly in lymphocyte development and human cancer progression. This review will summarize these new developments, while identifying significant unanswered questions and providing new hypotheses that may be addressed in future studies.

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Section: Additional Nf-κb Signaling By Genotoxic Agentsmentioning

confidence: 99%

Nuclear initiated NF-κB signaling: NEMO and ATM take center stage

2010

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“…In 2005, high constitutive nuclear levels of RelB were reported in prostate cancer (32). Furthermore, inhibition of RelB in an aggressive prostate cancer cell line significantly reduced the incidence and growth rate of the corresponding tumor xenografts (33).…”

Section: Req Binds To Subunits Of the Swi/snf Complex In Vitro Andmentioning

confidence: 99%

Requiem Protein Links RelB/p52 and the Brm-type SWI/SNF Complex in a Noncanonical NF-κB Pathway

Tando

Ishizaka

Watanabe

et al. 2010

Journal of Biological Chemistry

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The SWI/SNF chromatin remodeling complex plays pivotal roles in mammalian transcriptional regulation. In this study, we identify the human requiem protein (REQ/DPF2) as an adaptor molecule that links the NF-B and SWI/SNF chromatin remodeling factor. Through in vitro binding experiments, REQ was found to bind to several SWI/SNF complex subunits and also to the p52 NF-B subunit through its nuclear localization signal containing the N-terminal region. REQ, together with Brm, a catalytic subunit of the SWI/SNF complex, enhances the NF-Bdependent transcriptional activation that principally involves the RelB/p52 dimer. Both REQ and Brm were further found to be required for the induction of the endogenous BLC (CXCL13) gene in response to lymphotoxin stimulation, an inducer of the noncanonical NF-B pathway. Upon lymphotoxin treatment, REQ and Brm form a larger complex with RelB/p52 and are recruited to the BLC promoter in a ligand-dependent manner. Moreover, a REQ knockdown efficiently suppresses anchorageindependent growth in several cell lines in which the noncanonical NF-B pathway was constitutively activated. From these results, we conclude that REQ functions as an efficient adaptor protein between the SWI/SNF complex and RelB/p52 and plays important roles in noncanonical NF-B transcriptional activation and its associated oncogenic activity.The SWI/SNF (switch/sucrose-nonfermentable) chromatin remodeling complex has important functional roles in the epigenetic regulation of many organisms and regulates a wide variety of genes (1, 2). In mammals, this complex is an assembly of about nine polypeptides and contains a single molecule of either Brm or BRG1 but not both (3). These two proteins are the catalytic subunits that together with noncatalytic subunits, such as BAF170, BAF155, Ini1, BAF60a, and ␤-actin, drive the remodeling of nucleosomes via their ATP-dependent helicase activity (4). Evidence has now accumulated that the Brm-type and BRG1-type SWI/SNF complexes regulate a set of target promoters that do not fully overlap. Indeed, Brm and BRG1 show clear differences in their biological activities. For example, Brm-type, but not BRG1-type, SWI/SNF complexes are essential for the maintenance of gene expression driven by the long terminal repeats of murine leukemia virus (5, 6) and human immunodeficiency virus (7). Moreover, in gastrointestinal cells, Brm but not BRG1 can transactivate Cdx2-dependent villin expression, even though both proteins can interact with Cdx2 (8). Overall, the SWI/SNF complexes interact with various proteins, including transcriptional regulators, through the many specific and varied associations with their subunits. We previously demonstrated that among all of the dimers formed between Fos and Jun family proteins, which compose the representative transcription factor AP-1, the c-Fos/c-Jun heterodimer most efficiently recruits SWI/SNF complexes to AP-1-binding sites through its specific binding activity to the BAF60a SWI/SNF subunit (9).Like AP-1, the NF-B 3 is an important transcription facto...

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“…Using immunohistochemical studies, it has been demonstrated that all the members of the NF-kB family were expressed by normal prostate tissues, prostatic intraepithelial neoplasia and prostate cancer. However, only the nuclear localization of RelB correlated with the prostate cancer patient's Gleason scores (Lessard et al, 2005), suggesting that the level of RelB is associated with prostate cancer progression. In this study, we examined the role of RelB in prostate cancer cells in response to radiation.…”

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confidence: 96%

RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells

Josson

Fang

et al. 2005

Oncogene

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The relationship between NF-jB and resistance to radiation treatment in many tumor cell types has been generally well recognized. However, which members of the NF-jB family contribute to radiation resistance is unclear.In the present study, we demonstrate that RelB plays an important radioprotective role in aggressive prostate cancer cells, in part by the induction of antioxidant and antiapoptotic manganese superoxide dismutase (MnSOD) gene. RelB is both constitutively present and is inducible by radiation in aggressive prostate cancer cells. Using ectopically expressed dominant negative inhibitor, p100 mutant, and the siRNA approach, we demonstrate that selective inhibition of RelB significantly decreases the levels of MnSOD resulting in a significant increase in the sensitivity of prostate cancer cells to radiation treatment. These results demonstrate that RelB plays an important role in redox regulation of the cell and protects aggressive prostate cancer cells against radiation-induced cell death. Thus, inhibition of RelB could be a novel mechanism to radiosensitize prostate cancer.

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Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study

Cited by 137 publications

References 24 publications

Nuclear initiated NF-κB signaling: NEMO and ATM take center stage

Nuclear initiated NF-κB signaling: NEMO and ATM take center stage

Requiem Protein Links RelB/p52 and the Brm-type SWI/SNF Complex in a Noncanonical NF-κB Pathway

RelB regulates manganese superoxide dismutase gene and resistance to ionizing radiation of prostate cancer cells

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