CONSTITUTIVE ACTIVATION OF NF- Κ B IN PRIMARY ADULT T-Cell LEUKEMIA CELLS

Mori, Nozomu; Fujii, Masahiro; Ikeda, Shu‐ichi; Yamada, Yasuaki; Tomonaga, Masao; Ballard, Dean W.; Yamamoto, Naoki

doi:10.1097/00042560-199904010-00027

Cited by 203 publications

(309 citation statements)

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“…other groups indicates that p50/p50 homodimers are generally repressors of transcription (Mori et al, 1999;Udalova et al, 2000). However, there are several reports that support the ability of p50/p50 homodimers to activate transcription (Dechend et al, 1999;Kurland et al, 2001;Priel et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

Garzon¹,

Pichiorri²,

et al. 2007

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MicroRNAs (miRNAs) are small non-coding RNAs of 19-25 nucleotides that are involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. However, little is known about the role of miRNAs in granulopoiesis. Here, we report the expression of miRNAs in acute promyelocytic leukemia patients and cell lines during all-trans-retinoic acid (ATRA) treatment by using a miRNA microarrays platform and quantitative real time-polymerase chain reaction (qRT-PCR). We found upregulation of miR-15a, miR-15b, miR-16-1, let-7a-3, let-7c, let-7d, miR-223, miR-342 and miR-107, whereas miR-181b was downregulated. Among the upregulated miRNAs, miR-107 is predicted to target NFI-A, a gene that has been involved in a regulatory loop involving miR-223 and C/EBPa during granulocytic differentiation. Indeed, we have confirmed that miR-107 targets NF1-A. To get insights about ATRA regulation of miRNAs, we searched for ATRA-modulated transcription factors binding sites in the upstream genomic region of the let-7a-3/let-7b cluster and identified several putative nuclear factor-kappa B (NF-jB) consensus elements. The use of reporter gene assays, chromatin immunoprecipitation and site-directed mutagenesis revealed that one proximal NF-jB binding site is essential for the transactivation of the let-7a-3/let-7b cluster. Finally, we show that ATRA downregulation of RAS and Bcl2 correlate with the activation of known miRNA regulators of those proteins, let-7a and miR-15a/ miR-16-1, respectively.

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Section: Discussionmentioning

confidence: 99%

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

Garzon¹,

Pichiorri²,

et al. 2007

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“…Additionally, we show that inhibition of NF-nB by InBa-mt32 significantly inhibits AEG-1-induced augmentation in soft agar colony formation and invasion of HeLa cells. Several different tumor cell types, including leukemia, lymphoma, myeloma, melanoma, prostate, colon, breast, pancreas, glioma, and head and neck squamous cell carcinoma cell lines, as well as samples obtained from cancer patients, have been reported to express constitutively active NF-nB (15)(16)(17)(25)(26)(27). Inhibition of p65 by specific antisense oligonucleotides successfully reduced the growth of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Activation of the Nuclear Factor κB Pathway by Astrocyte Elevated Gene-1: Implications for Tumor Progression and Metastasis

Emdad¹,

Sarkar²,

Su³

et al. 2006

Cancer Research

258

355

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Astrocyte elevated gene-1 (AEG-1) was initially identified as an HIV-1-and tumor necrosis factor A (TNF-A)-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. Interestingly, AEG-1 expression is elevated in subsets of breast cancer, glioblastoma multiforme and melanoma cells and AEG-1 cooperates with Ha-ras to promote transformation of immortalized melanocytes. Activation of the transcription factor nuclear factor KB (NF-KB), a TNF-A downstream signaling component, is associated with several human illnesses, including cancer, and NF-KB controls the expression of multiple genes involved in tumor progression and metastasis. We now document that AEG-1 is a significant positive regulator of NF-KB. Enhanced expression of AEG-1 via a replication-incompetent adenovirus (Ad.AEG-1) in HeLa cells markedly increased binding of the transcriptional activator p50/p65 complex of NF-KB. The NF-KB activation induced by AEG-1 corresponded with degradation of IKBA and nuclear translocation of p65 that resulted in the induction of NF-KB downstream genes. Infection with an adenovirus expressing the mt32IKBA superrepressor (Ad.IKBA-mt32), which prevents p65 nuclear translocation, inhibited AEG-1-induced enhanced agar cloning efficiency and increased matrigel invasion of HeLa cells. We also document that TNF-A treatment resulted in nuclear translocation of both AEG-1 and p65 wherein these two proteins physically interacted, suggesting a potential mechanism by which AEG-1 could activate NF-KB. Our findings suggest that activation of NF-KB by AEG-1 could represent a key molecular mechanism by which AEG-1 promotes anchorage-independent growth and invasion, two central features of the neoplastic phenotype.

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“…A common and striking feature of ATL cells in late stages of the disease is the absence of detectable Tax expression, suggesting that Tax expression may no longer be required [99]. However, ATL cells appear to have acquired a ''Tax phenotype'': NF-kB and AP-1 are constitutively activated [100,101], p53 is stabilized and functionally impaired in the absence of mutations [102], and expression of p21 waf , survivin, and Bcl-xL is increased [103][104][105][106].…”

Section: Molecular Pathogenesismentioning

confidence: 99%

Current views in HTLV-I-associated adult T-cell leukemia/lymphoma

Nicot

2005

Am. J. Hematol.

104

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Epidemiological studies have demonstrated that the relative percentage of malignant lymphoid proliferations varies widely according to geographical location and ethnic populations. HTLV-I is the etiological agent of adult T-cell leukemia/lymphoma (ATLL) and is also associated with cutaneous T-cell lymphoma (CTCL). However, a definite role of HTLV-I in mycosis fungoides (MF) and/or Sezary syndrome (SS) remains controversial. While most HTLV-I-infected individuals remain asymptomatic carriers, 1-5% will develop ATLL, an invariably fatal expansion of virus-infected CD4 + T cells. This low incidence and the long latency period preceding occurrence of the disease suggest that additional factors are involved in development of ATLL. In this review, diagnosis, clinical features, and molecular pathogenesis of HTLV-I are discussed. Am.

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CONSTITUTIVE ACTIVATION OF NF- Κ B IN PRIMARY ADULT T-Cell LEUKEMIA CELLS

Cited by 203 publications

References 0 publications

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

MicroRNA gene expression during retinoic acid-induced differentiation of human acute promyelocytic leukemia

Activation of the Nuclear Factor κB Pathway by Astrocyte Elevated Gene-1: Implications for Tumor Progression and Metastasis

Current views in HTLV-I-associated adult T-cell leukemia/lymphoma

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