Brigitte Pützer

Brigitte Pützer
University Medical Center Rostock · Institute of Experimental Gene Therapy and Cancer Research

Prof. Dr. med. Dr. rer. nat.

About

196
Publications
15,718
Reads
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6,528
Citations
Additional affiliations
January 2004 - December 2012
Universität Rostock
January 2003 - present
University Hospital Essen
Position
  • Universität Duisburg-Essen
January 2002 - December 2005
Universitätsklinikum Essen

Publications

Publications (196)
Article
Full-text available
The transcription factor p73 is a structural and functional homolog of TP53, the most famous and frequently mutated tumor-suppressor gene. The TP73 gene can synthesize an overwhelming number of isoforms via splicing events in 5′ and 3′ ends and alternative promoter usage. Although it originally came into the spotlight due to the potential of severa...
Preprint
Skin melanoma presents increasing prevalence and poor outcomes. Progression to aggressive stages is characterized by overexpression of the transcription factor E2F1 and activation of downstream pro-metastatic gene regulatory networks (GRNs). Appropriate therapeutic manipulation of the E2F1-governed GRNs holds potential to prevent metastasis, howeve...
Conference Paper
Metastasis signals the final and treatment-refractory stage of cancer disease. Formation of metastases is fueled by a small cell subpopulation within the tumor, the so-called cancer stem cells (CSCs), which have the ability to rejuvenate the heterogeneous tumor population and support self-renewal, survival and tumor cell heterogeneity. Stemness is...
Article
Full-text available
Cancer acquires metastatic potential and evolves via co-opting gene regulatory networks (GRN) of embryonic development and tissue homeostasis. Such GRNs are encoded in the genome and frequently conserved among species. Considering that all metazoa have evolved from a common ancestor via major macroevolutionary events which shaped those GRNs and inc...
Article
Full-text available
Mechanisms governing tumor progression differ from those of initiation. One enigmatic prometastatic process is the recapitulation of pathways of neural plasticity in aggressive stages. Cancer and neuronal cells develop reciprocal interactions via mutual production and secretion of neuronal growth factors, neurothrophins and/or axon guidance molecul...
Article
Full-text available
Long non-coding RNAs (lncRNAs) have emerged as integral components of E2F1-regulated gene regulatory networks (GRNs), but their implication in advanced or treatment-refractory malignancy is unknown. Methods: We combined high-throughput transcriptomic approaches with bioinformatics and structure modeling to search for lncRNAs that participate in E2F...
Article
Full-text available
Double strand break (DSB) repair mechanisms guard genome integrity and their deterioration causes genomic instability. Common and rare fragile sites (CFS and RFS, respectively) are particularly vulnerable to instability, and there is an inverse correlation between fragile site (FS) expression and DSB repair protein levels. Upon DSB repair dysfuncti...
Article
Full-text available
Background: Bladder cancer progression has been associated with dysfunctional repair of double-strand breaks (DSB), a deleterious type of DNA lesions that fuel genomic instability. Accurate DSB repair relies on two distinct pathways, homologous recombination (HR) and classical non-homologous end-joining (c-NHEJ). The transcription factor E2F1 supp...
Article
Introduction: Functional disorders of the villous trophoblast may result in preeclampsia through the release of endothelial activating substances. Progranulin is an anti-inflammatory, pro-angiogenic cytokine with TNF-α antagonizing activity. The trophoblastic expression of progranulin is increased during preeclampsia. The aim of the study was to i...
Article
Full-text available
Melanoma is a skin cancer which can become metastatic, drug-refractory, and lethal if managed late or inappropriately. An increasing number of melanoma patients exhibits autoimmune diseases, either as pre-existing conditions or as sequelae of immune-based anti-melanoma therapies, which complicate patient management and raise the need for more perso...
Poster
Full-text available
INTRODUCTION • E2F1 overexpression across high-grade tumors culminates in unfavorable prognosis and chemoresistance in patients. METHODS • We integrated bioinformatics, structural and kinetic modelling, and experiments to study regulation of E2F1 by cooperative microRNAs (miRNAs) in the context of anticancer chemotherapy resistance. RESULTS • We us...
Article
Full-text available
Cytotoxic T lymphocyte (CTL) activation contributes to liver damage during sepsis, but the mechanisms involved are largely unknown. Understanding the underlying principle will permit interference with CTL activation and thus, provide a new therapeutic option. Methods: To elucidate the mechanism leading to CTL activation we used the Hepa1-6 cell li...
Article
Full-text available
Metastasis management remains a long-standing challenge. High abundance of E2F1 triggers tumor progression by developing protein-protein interactions (PPI) with coregulators that enhance its potential to activate a network of prometastatic transcriptional targets. Methods: To identify E2F1-coregulators, we integrated high-throughput Co-immunoprecip...
Chapter
Full-text available
The transcription factor p73 synthesizes a large number of isoforms and presents high structural and functional homology with p53, a well-known tumor suppressor and a famous “Holy Grail” of anticancer targeting. p73 has attracted increasing attention mainly because (a) unlike p53, p73 is rarely mutated in cancer, (b) some p73 isoforms can inhibit a...
Article
Melanoma is an aggressive cancer with poor prognosis, requiring personalized management of advanced stages and establishment of molecular markers. Melanomas derive from melanocytes, which specifically express tyrosinase, the rate-limiting enzyme of melanin-synthesis. We demonstrate that melanomas with high levels of DNp73, a cancer-specific variant...
Article
Metastasis is one of the most challenging issues in cancer patient management, and effective therapies to specifically target disease progression are missing, emphasizing the urgent need for developing novel antimetastatic therapeutics. Cancer stem cells (CSCs) gained fast attention as a minor population of highly malignant cells within liquid and...
Article
Cellular phenotypes are established and controlled by complex and precisely orchestrated molecular networks. In cancer, mutations and dysregulations of multiple molecular factors perturb the regulation of these networks and lead to malignant transformation. High-throughput technologies are a valuable source of information to establish the complex m...
Article
Full-text available
High rates of lethal outcome in tumour metastasis are associated with the acquisition of invasiveness and chemoresistance. Several clinical studies indicate that E2F1 overexpression across high-grade tumours culminates in unfavourable prognosis and chemoresistance in patients. Thus, fine-tuning the expression of E2F1 could be a promising approach f...
Article
Full-text available
Cancer is a disease of subverted regulatory pathways. In this paper, we reconstruct the regulatory network around E2F, a family of transcription factors whose deregulation has been associated to cancer progression, chemoresistance, invasiveness, and metastasis. We integrate gene expression profiles of cancer cell lines from two E2F1-driven highly a...
Article
Wnt/β-catenin and Wnt/Ca²⁺ pathways are involved in cellular processes during embryonic development and the interaction between them in the same cell decides the outcome of cellular functions. In this study, we showed that Wnt3a triggers the Wnt/Ca²⁺ signaling pathway, indicated by an increase of cytosolic free calcium ([Ca²⁺]i) and activation of c...
Article
Cancer progression to metastatic stages is still unmanageable and the promise of effective anti-metastatic therapy remains largely unmet, emphasizing the need to develop novel therapeutics. The special focus here is on cancer stem cells (CSC) as the seed of tumor initiation, epithelial-mesenchymal transition, chemoresistance and, as a consequence,...
Article
AIM: The therapeutic arsenal against muscle-invasive bladder cancer (BC) is poor, leading to fatal outcomes and necessitating next-generation targeted therapeutics. A causative event of BC progression is activation of the gene regulatory networks (GRN) of the transcription factor E2F1. LncRNAs are emerging integral components of the E2F1-regulated...
Article
Background: For penile cancer (PC) there are no known molecular predictors of lymphatic spread and/or chemoresistance. Objective: To identify functional biomarkers that can predict malignant progression and treatment responsiveness. Design, setting, and participants: We used four patient-derived PC cell lines and measured invasion and capillar...
Article
Full-text available
Background Dominant-activating mutations in the RET proto-oncogene, a receptor tyrosine kinase, are responsible for the development of medullary thyroid carcinoma (MTC) and causative for multiple endocrine neoplasia (MEN) type 2A and 2B. These tumors are highly aggressive with a high propensity for early metastasis and chemoresistance. This attribu...
Chapter
Increasing numbers of therapeutic genes and cellular targets are available for gene therapy. Many clinical trials using virus-derived delivery systems are devoted to combat cancer, to correct single-gene malfunctions or to regenerate tissues. To develop gene delivery vectors with high efficiency through target cell selectivity, in particular under...
Article
Tumour metastasis is considered to be one of the most important problems in cancer research and the identification of mechanisms that drive this multistep process provides urgently needed opportunities for therapeutic interventions. Many cancer types are driven by the dysfunction of transcriptional coregulators which interact with transcription fac...
Article
The transcription factor E2F1 is a key regulator of cell proliferation and apoptosis. Recently, it has been shown that aberrant E2F1 expression often detectable in advanced-stage metastatic and chemoresistant cancers contributes essentially to malignant progression and characterizes the aggressive potential of a tumor. Conceptually, this requires a...
Article
Direct induction of induced hepatocytes (iHeps) from fibroblasts holds potential as a strategy for regenerative medicine but until now has only been shown in culture settings. Here, we describe in vivo iHep formation using transcription factor induction and genetic fate tracing in mouse models of chronic liver disease. We show that ectopic expressi...
Article
Purpose: Penile squamous cell carcinoma (PSCC) is a rare but aggressive cancer and little is known about pivotal events in tumor pathogenesis and metastasis. Occurrence of lymph node metastases is the prevailing prognostic factor while their clinical detection in patients remains difficult. Our aim was to identify distinct miRNAs differentially ex...
Article
Full-text available
There is a distinct diversity between the appearance of every glioblastoma multiforme (GBM) on pretreatment magnetic resonance imaging (MRI) with a potential impact on clinical outcome and survival of the patients. The object of this study was to determine the impact of 10 different single nucleotide polymorphisms (SNPs) on various volumetric param...
Article
Cancer stem-like cells (CSC) have been proposed to promote cancer progression by initiating tumor growth at distant sites, suggesting that stem-like cell features can support metastatic efficiency. Here we demonstrate that oncogenic DNp73, a dominant-negative variant of the tumor suppressor p73, confers cancer cells with enhanced stem-like properti...
Article
Full-text available
Transcription factor E2F1 is a key regulator of cell proliferation and apoptosis. Recently, it has been shown that aberrant E2F1 expression often detectable in advanced cancers contributes essentially to cancer cell propagation and characterizes the aggressive potential of a tumor. Conceptually, this requires a subset of malignant cells capable of...
Article
Metastatic spread is the major cause of cancer-associated mortality and induced in primary tumor cells by the acquisition of mesenchymal features. Emerging evidence suggests that metastasis-initiating cancer cells undergoing epithelial-mesenchymal transition (EMT) possess stem cell-like traits. In this study, we demonstrate that oncogenic DNp73, an...
Article
Full-text available
We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by th...
Article
Full-text available
Neural stem/progenitor cells (NSPCs) have the potential to self-renew and to generate all neural lineages as well as to repopulate damaged areas in the brain. Our previous targeting strategies have indicated precursor cell heterogeneity between different brain regions that warrants the development of NSPC-specific delivery vehicles. Here, we demons...
Article
Full-text available
p73 is the older sibling of p53 and mimics most of its tumor-suppressor functions. Through alternative promoter usage and splicing, the TP73 gene generates more than two dozen isoforms of which N-terminal truncated DNp73 variants have a decisive role in cancer pathogenesis as they outweigh the positive effects of full-length TAp73 and p53 in acting...
Article
Dissemination of cancer cells from primary to distant sites is a complex process; little is known about the genesis of metastatic changes during disease development. Here we show that the metastatic potential of E2F1-dependent circulating tumor cells cphCTCs) relies on a novel function of the hyaluronan-mediated motility receptor RHAMM. E2F1 direct...
Article
Malignant melanoma is highly lethal due to its aggressive invasive properties and metastatic dissemination. The transcription factor E2F1 is crucial for melanoma progression through poorly understood mechanisms. Here, we show that the miR-224/miR-452 cluster is significantly increased in advanced melanoma and invasive/metastatic cell lines that exp...
Article
The prevailing view has been that N-terminally truncated p53 family isoforms (ΔNp53, ΔNp63, and DNp73) predominantly counteract cell cycle arrest and apoptosis. Recent progress in the field extend these well-known functions and place these isoforms in the center of a comprehensive regulatory network controlling major epithelial-to-mesenchymal trans...
Article
Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem-cell like cells in liver regeneration. Lhx2 is...
Article
Dissemination of cancer cells from primary to distant sites is a complex process; little is known about the genesis of metastatic changes during disease development. Here we show that the metastatic potential of E2F1-dependent circulating tumor cells (CTCs) relies on a novel function of the hyaluronan-mediated motility receptor RHAMM. E2F1 directly...
Article
Full-text available
Due to the fundamental progress in elucidating the molecular mechanisms of human diseases and the arrival of the post-genomic era, increasing numbers of therapeutic genes and cellular targets are available for gene therapy. Meanwhile, the most important challenge is to develop gene delivery vectors with high efficiency through target cell selectivi...
Article
Full-text available
Malignant melanoma is a highly aggressive cancer that retains functional p53 and p73, and drug unresponsiveness largely depends on defects in death pathways after epigenetic gene silencing in conjunction with an imbalanced p73/DNp73 ratio. We constructed oncolytic viruses armed with an inhibitor of deacetylation and/or p73 to specifically target me...