A5037722440- Liver Disease Diagnosis and Treatment
- Growth Hormone and Insulin-like Growth Factors
- Liver physiology and pathology
- Cancer Cells and Metastasis
- Hedgehog Signaling Pathway Studies
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Cytokine Signaling Pathways and Interactions
- Cancer Mechanisms and Therapy
- Viral Infectious Diseases and Gene Expression in Insects
- Wnt/β-catenin signaling in development and cancer
- Animal Genetics and Reproduction
- PI3K/AKT/mTOR signaling in cancer
- Liver Diseases and Immunity
- Virus-based gene therapy research
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- Mechanisms of cancer metastasis
- Lipid metabolism and disorders
- Cancer, Stress, Anesthesia, and Immune Response
- Cell death mechanisms and regulation
- Caveolin-1 and cellular processes
Karolinska Institutet
2014-2024
Ludwig Boltzmann Institute for Cancer Research
2007-2019
Inserm
2009
Université de Rennes
2009
Paracelsus Medical University
2006
University of Amsterdam
1991
Hedgehog (HH)/GLI signaling plays a critical role in epidermal development and basal cell carcinoma. Here, we provide evidence that growth factor receptor (EGFR) modulates the target gene expression profile of GLI transcription factors cells. Using profiling quantitative reverse transcriptase PCR, identified set 19 genes whose is synergistically induced by GLI1 parallel EGF treatment. Promoter studies subset GLI/EGF-regulated genes, including encoding interleukin-1 antagonist IL1R2, Jagged...
Abstract STAT3 is considered to play an oncogenic role in several malignancies including lung cancer; consequently, targeting currently proposed as therapeutic intervention. Here we demonstrate that plays unexpected tumour-suppressive KRAS mutant adenocarcinoma (AC). Indeed, tissue-specific inactivation of Stat3 mice results increased Kras G12D -driven AC initiation and malignant progression leading markedly reduced survival. Knockdown xenografted human cells increases tumour growth....
Abstract A role for Hedgehog (Hh) signalling in the development of colorectal cancer (CRC) has been proposed. In CRC and other solid tumours, Hh ligands are upregulated; however, a specific antagonist provided no benefit clinical trial. Here we use reporter mice to show that downstream activity is unexpectedly diminished mouse model colitis-associated colon cancer, restricted stroma. Functionally, stroma-specific activation markedly reduces tumour load blocks progression advanced neoplasms,...
Growth hormone (GH)-activated signal transducer and activator of transcription 5 (STAT5) the glucocorticoid (GC)-responsive receptor (GR) are important integrators in liver during metabolic physiologic stress. Their deregulation has been implicated development diseases, such as steatosis progression to fibrosis. Using liver-specific STAT5 GR knockout mice, we addressed their role metabolism cancer onset. single STAT5/GR double mutants developed steatosis, but only double-mutant mice...
The gene desert upstream of the MYC oncogene on chromosome 8q24 contains susceptibility loci for several major forms human cancer. region shows high conservation between and mouse multiple enhancers that are activated in tumor cells. However, role this normal development has not been addressed. Here we show a 538 kb deletion entire super-enhancer mice results 50% to 80% decrease Myc expression tissues. viable no overt phenotype. they resistant tumorigenesis, most cells isolated from them...
The structure of the receptor for fimbriae Haemophilus influenzae on human oropharyngeal epithelial cells and erythrocytes was determined in inhibition experiments with various sugars, glycolipids, glycoproteins. Of 30 monosaccharides disaccharides at a concentration 0.1 M 3 polysaccharides 1 mg/ml, none inhibited fimbria-specific adherence hemagglutination. Inhibition obtained gangliosides GM1, GM2, GM3, GD1a nanomolar concentrations, whereas asialo derivative sialyl-lactose,...
Growth hormone (GH) resistance and low serum levels of insulinlike growth factor 1 (IGF-1) are common features in human liver fibrosis cirrhosis. Signal transducer activator transcription 5 (STAT5) controls several vital functions the liver, including GH-mediated IGF-1. To investigate role STAT5 fibrogenesis, we specifically deleted Stat5a/b locus both hepatocytes cholangiocytes multidrug gene 2 knockout (Mdr2−/−) mouse model cholestasis. Double mice develop an early severe phenotype,...
Growth hormone (GH) resistance has been associated with liver cirrhosis in humans but its contribution to the disease remains controversial. In order elucidate whether GH plays a causal role establishment and development of fibrosis, or rather represents major consequence thereof, we challenged mice lacking receptor gene (Ghr –/– , model for resistance) by crossing them Mdr2 knockout (Mdr2 ), mouse inflammatory cholestasis fibrosis. Ghr ;Mdr2 showed elevated serum markers damage cholestasis,...
The development of appropriate expression vectors for large scale protein production constitutes a critical step in recombinant production. use conventional to obtain cell lines is cumbersome procedure. Often, stable produce low yields and not over the time. These problems are due silencing randomly integrated by surrounding chromatin. To overcome these chromatin effects, we have employed Bacterial Artificial Chromosome (BAC) as vector suitable production.In this work, explore efficacy based...
Epithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet exact roles of specific BM components remain unclear. Here, we show that Laminin α5 (Lama5) expression specifically in luminal epithelial cells necessary normal growth during puberty, and alveologenesis pregnancy. Lama5 loss keratin 8-expressing results reduced frequency differentiation hormone receptor expressing (HR+) cells. Consequently, Wnt4-mediated crosstalk between HR+ basal compromised...
The use of bacterial artificial chromosomes (BACs) modified via homologous recombination in Escherichia coli has become a powerful tool the transgenic field. Homologous allows manipulation BACs very different ways. However, this process can be cumbersome and problematic when using large targeting constructs containing several repeated elements. In order to address problem, we have established ΦC31 integrase-mediated cassette exchange into BAC. As an example technique, exchanged previously...
Here we describe the generation of an inducible Cre transgenic line allowing conditional mutagenesis in ovarian granulosa cells. We have expressed tamoxifen CreER(T)² fusion protein from a Bacterial Artificial Chromosome (BAC) containing regulatory elements hydroxysteroid (17-beta) dehydrogenase 1 (Hsd17b1) gene. Hsd17b1-iCreER(T)² mice express iCreER(T)² exclusively Recombination analysis at genomic DNA level using with "floxed" Stat3 alleles showed no activity absence whereas treatment...
ABSTRACT Basement membrane (BM) supports and regulates the structural integrity, function differentiation of epithelial tissues protects against stromal invasion breast cancer cells. Here we show that LAMA5, a central BM component, is critical for luminal mammary tumour initiation, controls tumor progression phenotype development. LAMA5 overexpressed in both human mouse tumours downregulation attenuates growth Prepubertal deletion Lama5 MMTV-PyMT mice results marked reduction emergence early...
Genetically-engineered mouse models (GEMMs) lacking diseased-associated gene(s) globally or in a tissue-specific manner represent an attractive tool with which to assess the efficacy and toxicity of targeted pharmacological inhibitors. Stat3 Stat5a/b transcription factors have been implicated several pathophysiological conditions, inhibition both has proposed treat certain diseases, such as malignancies. To model combined we developed GEMM harboring flox Stat3-Stat5a/b allele...
ABSTRACT Epithelial attachment to the basement membrane (BM) is essential for mammary gland development, yet exact roles of specific BM components remain unclear. Here, we demonstrate that expression distinct laminin α-isoforms by luminal and basal epithelial cells enforces lineage identity necessary normal growth function. Laminin α5 (LMα5) mainly expressed cells, it pubertal growth, pregnancy induced remodeling, alveolar Adhesion LMα5 containing promotes traits in both reduces progenitor...
Abstract Liver fibrosis is defined as the pathological excessive deposition of extracellular matrix proteins which contributes to a disruption normal liver architecture. Fibrosis can progress cirrhosis, eventually result in hepatocellular carcinoma. Over past decades our understanding cellular and molecular mechanisms has advanced greatly. Activated hepatic stellate cells, myofibroblasts bone marrow origin portal fibroblasts have all been identified major contributors fibrosis. Recently,...
Abstract The gene desert upstream of the Myc oncogene on chromosome 8q24 contains susceptibility loci for several major forms human cancer, including cancers breast, prostate, and colon. region shows high conservation between mouse multiple MYC enhancers that are activated in tumor cells. However, role this normal development has not been addressed. Here we show a 538 kb deletion entire super-enhancer mice results 50 to 80% decrease expression tissues. viable no overt phenotype. they...