Interferon Regulatory Factor 4 Contributes to Transformation of v-Rel-Expressing Fibroblasts

Hrdličková, Radmila; Nehyba, Jiřı́; Bose, Henry R.

doi:10.1128/mcb.21.19.6369-6386.2001

Cited by 33 publications

(16 citation statements)

References 111 publications

(120 reference statements)

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“…The expression of IRF4 has been shown to be upregulated in v-Rel-expressing cells, and an increased expression level of IRF4 plays a role in the v-Relmediated transformation process. (146) Similarly to IRF8 described above, there are also several reports suggesting a possible role of IRF4 in the pathogenesis of CML. The expression level of IRF4 is significantly low in CML patients.…”

Section: Oncogenic Irfmentioning

confidence: 73%

Interferon regulatory factor family of transcription factors and regulation of oncogenesis

Takaoka¹,

Tamura²,

Taniguchi³

2008

Cancer Science

134

115

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Section: Oncogenic Irfmentioning

confidence: 73%

Interferon regulatory factor family of transcription factors and regulation of oncogenesis

Takaoka¹,

Tamura²,

Taniguchi³

2008

Cancer Science

134

115

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“…Transforming activity of MUM1 has been recognized in a fibroblast cell line, Rat-1, and primary chicken embryonic fibroblasts. 15,46) Thus, MUM1 expression may induce the growth of leukemic cells and may result in aggressive clinical behavior. Additionally, Bechter et al 47) reported that the telomere length and telomerase activity were correlated with survival among patients with B-CLL.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, Bechter et al 47) reported that the telomere length and telomerase activity were correlated with survival among patients with B-CLL. Since MUM1 has been suggested to extend the lifespan of chicken primary embryonic fibroblasts, 46) its expression could delay senescence of tumor cells. The relationship between MUM1 and telomerase activity needs to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

MUM1/IRF4 Expression Is an Unfavorable Prognostic Factor in B‐Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Ito

Iida

Inagaki

et al. 2002

Japanese Journal of Cancer Research

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B-Cell chronic lymphocytic leukemia (B-CLL)/small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B-CLL/SLL, and found that 2 of 4 B-CLL-derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgV H ), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival times than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P = = = =0.0008, log-rank test). Multivariate analysis by Cox's proportional-hazards regression model showed that MUM1 expression and unmutated IgV H status were independent unfavorable prognostic factors in patients with B-CLL/SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B-CLL/SLL. The biological role and mechanism of action of MUM1 in B-CLL/SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype.

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“…It differs from other IRFs in several ways including its repressive effect on IFN-induced gene expression [5,32] and induction by proliferative stimuli [5,33]. These and other unique effects [5,[10][11][12]34] culminate into an oncogenic activity [13]. Most B-cell malignancies have increased IRF4…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males

Thuy¹,

Ucisik-Akkaya²,

Davis³

et al. 2010

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The interferon regulatory factor (IRF) family of DNA-binding proteins regulates expression of interferon-inducible genes with roles in the immune response and carcinogenesis. IRF4 is involved in the differentiation of B and T cells and is overexpressed in B-cell malignancies as a result of c-REL (NF-kappaB) hyperactivation. IRF4 polymorphisms are associated with susceptibility to chronic lymphoid leukemia (CLL) and non-Hodgkin lymphoma (NHL). We examined 13 IRF4 SNPs in 114 cases of childhood acute lymphoblastic leukemia (ALL) and 388 newborn controls from Wales (U.K.) using TaqMan assays. IRF4 intron 4 SNP rs12203592 showed a male-specific risk association (OR=4.4, 95% CI=1.5 to 12.6, P=0.007). Functional consequences of the C>T substitution at this SNP were assessed by cell-based reporter assays using three different cell lines. We found a repressive effect of the rs12203592 wildtype allele C on IRF4 promoter activity (P<0.001) but no repression by the variant allele in any cell line tested. Thus, homozygosity for the rs12203592 variant allele would result in increased IRF4 expression. This increase would be compounded by high levels of NF-kappaB activity in males due to the absence of estrogen. IRF4 differs from other IRFs in its anti-interferon activity which interferes with immune surveillance. We propose that a detailed study of IRF4 can provide information on the mechanism of the sex effect and the role of immune surveillance in childhood ALL development.

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Interferon Regulatory Factor 4 Contributes to Transformation of v-Rel-Expressing Fibroblasts

Cited by 33 publications

References 111 publications

Interferon regulatory factor family of transcription factors and regulation of oncogenesis

Interferon regulatory factor family of transcription factors and regulation of oncogenesis

MUM1/IRF4 Expression Is an Unfavorable Prognostic Factor in B‐Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

An intronic polymorphism of IRF4 gene influences gene transcription in vitro and shows a risk association with childhood acute lymphoblastic leukemia in males

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