Search results for "Tyro"
showing 10 items of 816 documents
β1-Integrin Cytoplasmic Subdomains Involved in Dominant Negative Function
1998
The beta1-integrin cytoplasmic domain consists of a membrane proximal subdomain common to the four known isoforms ("common" region) and a distal subdomain specific for each isoform ("variable" region). To investigate in detail the role of these subdomains in integrin-dependent cellular functions, we used beta1A and beta1B isoforms as well as four mutants lacking the entire cytoplasmic domain (beta1TR), the variable region (beta1COM), or the common region (beta1 deltaCOM-B and beta1 deltaCOM-A). By expressing these constructs in Chinese hamster ovary and beta1 integrin-deficient GD25 cells (Wennerberg et al., J Cell Biol 132, 227-238, 1996), we show that beta1B, beta1COM, beta1 deltaCOM-B, a…
Expression Of FLT3-ITD Dysregulates The DBC1-Sirt1-p53 Signaling and Promotes Therapy Resistance
2013
Abstract Background SIRT1 is a NAD+ dependent histone deacetylase, which has been shown to act as an important regulator of apoptosis, DNA-repair and is involved in the maintenance of genetic integrity under conditions of cellular stress. Beside deacetylation of histones H4K16, SIRT1 has numeral other substrates including KU70, FOXO1 or p53. SIRT1 deacetylates p53 at lysine 382 thereby reducing its transcriptional activity followed by loss of p53 dependent apoptosis in response to cell damage. The activity of SIRT1 is negatively regulated by DBC1 (Deleted in Breast Cancer 1) and involves protein–protein interaction (Kim et al., Nature 2008). Recent reports have demonstrated increased expres…
EGFR genomic alterations in cancer: prognostic and predictive values.
2011
The role of EGFR in cancer development and progression has been recognized for long time in a variety of human malignancies including lung, head and neck, colon, breast, ovary and glioma. Recently its role as a target of antineoplastic agents has also been identified and a variety of EGFR-targeted drugs is already being used in a clinical setting and others are at present under investigation. Many data involving EGFR protein expression are now available for the choice of anti-EGFR monoclonal antibodies in colorectal cancer and with regard to EGFR gene mutations for the choice of tyrosine kinase inhibitors in lung cancer. Other EGFR-related molecular factors, including the EGFR gene copy num…
Comparative architectural aspects of regions of conserved synteny on human chromosome 11p15.3 and mouse chromosome 7 (including genes WEE1 and LMO1)
2001
Human chromosome 11p15.3 is associated with chromosome aberrations in the Beckwith Wiedemann Syndrome and implicated in the pathogenesis of different tumor types including lung cancer and leukemias. To date, only single tumor-relevant genes with linkage to this region (e.g. LMO1) have been found suggesting that this region may harbor additional potential disease associated genes. Although this genomic area has been studied for years, the exact order of genes/chromosome markers between D11S572 and the WEE1 gene locus remained unclear. Using the FISH technique and PAC clones of the flanking markers we determined the order of the genomic markers. Based on these clones we established a PAC cont…
Inhibition of the HER2 pathway by n-3 polyunsaturated fatty acids prevents breast cancer in fat-1 transgenic mice
2013
Overexpression of the tyrosine kinase receptor, ErbB2/HER2/Neu, occurs in 25–30% of invasive breast cancer (BC) with poor patient prognosis. Due to confounding factors, inconsistencies still remain regarding the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on BC. We therefore evaluated whether fat-1 transgenic mice, endogenously synthesizing n-3 PUFAs from n-6 PUFAs, were protected against BC development, and we then aimed to study in vivo a mechanism potentially involved in such protection. E0771 BC cells were implanted into fat-1 and wild-type (WT) mice. After tumorigenesis examination, we analyzed the expression of proteins involved in the HER2 signaling pathway and lipi…
n-3 polyunsaturated fatty acids and HER2-positive breast cancer: interest of the fat-1 transgenic mouse model over conventional dietary supplementati…
2013
Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25%-30% of invasive breast cancer (BC) with poor patient prognosis. Even if numerous studies have shown prevention of breast cancer by n-3 fatty acid intake, the experimental conditions under which n-3 fatty acids exert their protective effect have been variable from study to study, preventing unifying conclusions. Due to confounding factors, inconsistencies still remain regarding protective effects of n-3 polyunsaturated fatty acids (PUFA) on BC. When animals are fed with dietary supplementation in n-3 fatty acids (the traditional approach to modify tissue content and decrease the n-6/n-3 ratio) complex dietary intera…
Spontaneous hepatic fibrosis in transgenic mice overexpressing PDGF-A.
2008
Platelet derived growth factor (PDGF) plays a central role in repair mechanisms after acute and chronic tissue damage. To further evaluate the role of PDGF-A in liver fibrogenesis in vivo, we generated transgenic mice with hepatocyte-specific overexpression of PDGF-A using the CRP-gene promoter. Transgenic but not wildtype mice showed expression of PDGF-A mRNA in the liver. Hepatic PDGF-A overexpression was accompanied by a significant increase in hepatic procollagen III mRNA expression as well as TGF-beta1 expression. Liver histology showed increased deposition of extracellular matrix in transgenic but not in wildtype mice. PDGF-A-transgenic mice showed positive sinusoidal staining for alp…
Sciences within European Young Researcher Community272The neuro-cardiac interaction defines an extracellular microdomain required for neurotrophic si…
2016
# 272 The neuro-cardiac interaction defines an extracellular microdomain required for neurotrophic signaling {#article-title-2} Purpose: Sympathetic neurons (SNs) innervate the myocardium with a defined topology that allows physiological modulation of cardiac activity. Limiting amounts of neurotrophins released by cardiac cells control SN viability and myocardial distribution, whose impairment has been described in a number of heart diseases (e.g. myocardial infarction, heart failure). Therefore, the fine control of cardiac innervation is crucial to ensure the physiological sympathetic function. It has been demonstrated that SNs directly interact with cardiomyocytes (CMs). Although it has b…
Non-small cell lung cancer (NSCLC), EGFR downstream pathway activation and TKI targeted therapies sensitivity: Effect of the plasma membrane-associat…
2017
Adenocarcinoma of Non-Small Cell Lung Cancer (NSCLC) is a severe disease. Patients carrying EGFR mutations may benefit from EGFR targeted therapies (e.g.: gefitinib). Recently, it has been shown that sialidase NEU3 directly interacts and regulates EGFR. In this work, we investigate the effect of sialidase NEU3 overexpression on EGFR pathways activation and EGFR targeted therapies sensitivity, in a series of lung cancer cell lines. NEU3 overexpression, forced after transfection, does not affect NSCLC cell viability. We demonstrate that NEU3 overexpression stimulates the ERK pathway but this activation is completely abolished by gefitinib treatment. The Akt pathway is also hyper-activated upo…
Gene structure and function of tyrosine kinases in the marine sponge Geodia cydonium: Autapomorphic characters of Metazoa
1999
Abstract Porifera (sponges) represent the most ancient, extant metazoan phylum. They existed already prior to the ‘Cambrian Explosion’. Based on the analysis of aa sequences of informative proteins, it is highly likely that all metazoan phyla evolved from only one common ancestor (monophyletic origin). As ‘autapomorphic’ proteins which are restricted to Metazoa only, integrin receptors, receptors with scavenger receptor cysteine-rich repeats, neuronal-like receptors and protein–tyrosine kinases (PTKs) have been identified in Porifera. From the marine sponge Geodia cydonium , a receptor tyrosine kinase (RTK) has been cloned that comprises the characteristic structural topology known from oth…