Immunohistochemical Expression of the Transcription Factor DP-1 and Its Heterodimeric Partner E2F-1 in Non-Hodgkin Lymphoma

Chan, Joel A.; Olvera, Maria; Lai, Raymond; Naing, Win; Rezk, Sherif; Brynes, Russell K.

doi:10.1097/00129039-200212000-00006

Cited by 8 publications

(7 citation statements)

References 24 publications

(21 reference statements)

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“…In the present study, E2F1 was expressed in 5/20 (25%) of reactive follicular hyperplasia cases mainly localized to the proliferating germinal center and few in the interfollicular areas with complete negativity in the mantle zone lymphocytes. Our results agreed with other reports that stated that E2F1 is a transcription factor that mediates cell-cycle progression from the G1 to S phase and is normally regulated by a group of proteins, including cyclin D1, mainly in the germinal center [ 31 , 32 ].…”

Section: Discussionsupporting

confidence: 93%

The Prognostic Role and Relationship between E2F1 and SV40 in Diffuse Large B-Cell Lymphoma of Egyptian Patients

Samaka

Aiad

Kandil

et al. 2015

Analytical Cellular Pathology

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Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphomas worldwide. The pathogenesis of lymphomas is not yet well understood. SV40 induces malignant transformation by the large T-antigen (L-TAG) and promotes transformation by binding and inactivating p53 and pRb. L-TAG can bind pRb promoting the activation of the E2F1 transcription factor, thus inducing the expression of genes required for the entry to the S phase and leading to cell transformation. This immunohistochemical study was conducted to assess the prognostic role and relationship of SV40 L-TAG and E2F1 in diffuse large B-cell lymphoma (DLBCL) of Egyptian patients. This retrospective study was conducted on 105 tissue specimens including 20 follicular hyperplasia and 85 DLBCL cases. SV40 L-TAG was identified in 3/85 (4%) of DLBCL. High Ki-67 labeling index (Ki-67 LI) and apoptotic count were associated with high E2F1 expression (p<0.001 for all). No significant association was reached between E2F1 and SV40. E2F1 expression proved to be the most and first independent prognostic factor on overall survival of DLBCL patients (HR = 5.79, 95% CI = 2.3–14.6, and p<0.001). Upregulation of E2F1 has been implicated in oncogenesis, prognosis, and prediction of therapeutic response but is not seemingly to have a relationship with the accused SV40.

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Section: Discussionsupporting

confidence: 93%

The Prognostic Role and Relationship between E2F1 and SV40 in Diffuse Large B-Cell Lymphoma of Egyptian Patients

Samaka

Aiad

Kandil

et al. 2015

Analytical Cellular Pathology

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“…Indeed, E2F is a known regulator of DNA replication and mitotic events (Ishida et al, 2001). In bladder carcinoma, the expression of TFDP1, an E2F dimerization partner (Chan et al, 2002), shows a significant correlation with the expression of E2F target genes in “mitosis”, “DNA replication” and “microtubule biogenesis” (see Figure S2C). We also predicted a potential association between AhR transcription factor and “ubiquitin-dependent protein degradation”.…”

Section: Resultsmentioning

confidence: 99%

Revealing Global Regulatory Perturbations across Human Cancers

2009

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Summary The discovery of pathways and regulatory networks whose perturbation contributes to neoplastic transformation remains a fundamental challenge for cancer biology. We show that such pathway perturbations, and the cis-regulatory elements through which they operate, can be efficiently extracted from global gene-expression profiles. Our approach utilizes information-theoretic analysis of expression levels, pathways, and genomic sequences. Analysis across a diverse set of human cancers reveals the majority of previously known cancer pathways. Through de novo motif discovery we associate these pathways with transcription-factor binding sites and miRNA targets, including those of E2F, NF-Y, p53, and let-7. Follow-up experiments confirmed that these predictions correspond to functional in vivo regulatory interactions. Strikingly, the majority of the perturbations, associated with putative cis-regulatory elements, fall outside of known cancer pathways. Our study provides a systems-level dissection of regulatory perturbations in cancer—an essential component of a rational strategy for therapeutic intervention and drug-target discovery.

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“…While several of these genes were previously reported as overexpressed in hematologic malignancies, such as MYC (34), FOXM1 (35), TFDP1 (36) or ATF5 (37), the majority of inferred MRs were not previously causally associated with FL transformation nor were they shown to represent individual/synergistic dependencies of transformed DLBCL. Five of these MRs emerged as the strongest causal determinant of FL-transformation signature, including FOXM1, TFDP1, ATF5, HMGA1, MYC and NFYB .…”

Section: Discussionmentioning

confidence: 99%

“…TFDP1 is an established heterodimerization partner of E2F family proteins, regulating transcriptional activity of cell cycle progression genes (40). Both TFDP1 and E2F1 can interact and inhibit transcriptional activity of p53 and are expressed in non-Hodgkin lymphomas (36). A member of the E2F family, E2F3, was also inferred as an activated MR by MARINa analysis suggesting that these proteins may represent interacting partners in FL progression.…”

Section: Discussionmentioning

confidence: 99%

Elucidation and Pharmacological Targeting of Novel Molecular Drivers of Follicular Lymphoma Progression

et al. 2016

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Follicular lymphoma (FL), the most common indolent subtype of non-Hodgkin’s lymphoma, is associated with a relatively long overall survival rate ranging from 6 to 10 years from time of diagnosis. However, in 20–60% of FL patients, transformation to aggressive diffuse large B-cell lymphoma (DLBCL) reduces median survival to only 1.2 years. The specific functional and genetic determinants of FL transformation remain elusive, and genomic alterations underlying disease advancement have only been identified for a subset of cases. Therefore, to identify candidate drivers of FL transformation, we performed systematic analysis of a B-cell-specific regulatory model exhibiting FL transformation signatures using the Master Regulator Inference algorithm (MARINa). This analysis revealed FOXM1, TFDP1, ATF5, HMGA1, and NFYB to be candidate master regulators (MR) contributing to disease progression. Accordingly, validation was achieved through synthetic lethality assays in which RNAi-mediated silencing of MRs individually or in combination reduced the viability of (14;18)-positive DLBCL (t-DLBCL) cells. Furthermore, specific combinations of small molecule compounds targeting synergistic MR pairs induced loss of viability in t-DLBCL cells. Collectively, our findings indicate that MR analysis is a valuable method for identifying bona fide contributors to FL transformation and may therefore guide the selection of compounds to be used in combinatorial treatment strategies.

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Immunohistochemical Expression of the Transcription Factor DP-1 and Its Heterodimeric Partner E2F-1 in Non-Hodgkin Lymphoma

Cited by 8 publications

References 24 publications

The Prognostic Role and Relationship between E2F1 and SV40 in Diffuse Large B-Cell Lymphoma of Egyptian Patients

The Prognostic Role and Relationship between E2F1 and SV40 in Diffuse Large B-Cell Lymphoma of Egyptian Patients

Revealing Global Regulatory Perturbations across Human Cancers

Elucidation and Pharmacological Targeting of Novel Molecular Drivers of Follicular Lymphoma Progression

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