Search results for "Tumor suppressor"
showing 10 items of 401 documents
WWOX-related encephalopathies: delineation of the phenotypical spectrum and emerging genotype-phenotype correlation
2014
International audience; BACKGROUND:Homozygous mutations in WWOX were reported in eight individuals of two families with autosomal recessive spinocerebellar ataxia type 12 and in two siblings with infantile epileptic encephalopathy (IEE), including one who deceased prior to DNA sampling.METHODS:By combining array comparative genomic hybridisation, targeted Sanger sequencing and next generation sequencing, we identified five further patients from four families with IEE due to biallelic alterations of WWOX.RESULTS:We identified eight deleterious WWOX alleles consisting in four deletions, a four base-pair frameshifting deletion, one missense and two nonsense mutations. Genotype-phenotype correl…
Wee1 inhibition potentiates Wip1-dependent p53-negative tumor cell death during chemotherapy
2016
AbstractInactivation of p53 found in more than half of human cancers is often associated with increased tumor resistance to anti-cancer therapy. We have previously shown that overexpression of the phosphatase Wip1 in p53-negative tumors sensitizes them to chemotherapeutic agents, while protecting normal tissues from the side effects of anti-cancer treatment. In this study, we decided to search for kinases that prevent Wip1-mediated sensitization of cancer cells, thereby interfering with efficacy of genotoxic anti-cancer drugs. To this end, we performed a flow cytometry-based screening in order to identify kinases that regulated the levels of γH2AX, which were used as readout. Another criter…
Apoptosis and cell cycle aberrations in epithelial odontogenic lesions : an evidence by the expression of p53, Bcl-2 and Bax
2017
Background Ameloblastoma (AMB), odontogenic keratocyst (OKC) and adenomatoid odontogenic tumor (AOT) are epithelial odontogenic lesions with diverse biologic profiles. Defects in regulation of apoptosis and cell cycle may be involved in the development and progression of those lesions, therefore we aimed to investigate the expression of Bcl-2, Bax and p53 to better understand the possible role of these proteins in AMBs, OKCs and AOTs. Material and Methods The studied sample consisted of 20 AMBs, 20 OKCs and 20 AOTs. Immunohistochemistry technique was performed for the antibodies p53, Bcl-2 and Bax. Immunoreactivity was observed in the epithelial component and positive cells were counted in …
Sequence-specific and DNA structure-dependent interactions of Escherichia coli MutS and human p53 with DNA
2013
Many proteins involved in DNA repair systems interact with DNA that has structure altered from the typical B-form helix. Using magnetic beads to immobilize DNAs containing various types of structures, we evaluated the in vitro binding activities of two well-characterized DNA repair proteins, Escherichia coli MutS and human p53. E. coli MutS bound to double-stranded DNAs, with higher affinity for a G/T mismatch compared to a G/A mismatch and highest affinity for larger non-B-DNA structures. E. coli MutS bound best to DNA between pH 6 and 9. Experiments discriminated between modes of p53-DNA binding, and increasing ionic strength reduced p53 binding to nonspecific double-stranded DNA, but had…
Role of Nitric Oxide for Modulation of Cancer Therapy Resistance
2010
Reactive nitrogen species (RNS) act as central second messengers in a balanced cellular network. While the complexity of nitric oxide (NO) signaling is far from being understood, and many controversial data can be found in the literature, there is evidence for NO as a major player of modulation of resistance to anticancer drugs and radiotherapy. Hypoxia in cancer tissues causes therapy resistance, and the hypoxia-inducing factor-1 (HIF-1) plays a predominant role in hypoxia-induced resistance. NO and NO-donating compounds sensitize tumor cells by inhibiting HIF-1 mediated transcription in hypoxic cells. Among a plethora of other genes, HIF-1-induced the transcription of the multidrug resist…
Functional Assessment of Variants in the TSC1 and TSC2 Genes Identified in Individuals with Tuberous Sclerosis Complex
2011
The effects of missense changes and small in-frame deletions and insertions on protein function are not easy to predict, and the identification of such variants in individuals at risk of a genetic disease can complicate genetic counselling. One option is to perform functional tests to assess whether the variants affect protein function. We have used this strategy to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC). Here we present an overview of our functional studies on 45 TSC1 and 107 TSC2 variants. Using a standardized protocol we classified 16 TSC1 variants and 70 TSC2 variants as pathogenic. In add…
RASSF1A inhibits estrogen receptor alpha expression and estrogen-independent signalling: implications for breast cancer development
2012
The Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor whose inactivation is implicated in the development of many human cancers, including breast carcinomas. Little is known about the tumor-suppressive function of RASSF1A in breast tissue and whether its inactivation is mechanistically involved in the initiation and progression of breast tumors. Here, we show that RASSF1A inhibits breast cancer growth in vivo, and suppresses estrogen receptor (ERα) expression and function. Reconstitution of RASSF1A in MCF7 cells led to decreased ERα levels and reduced sensitivity to estrogen (E2). Concomitantly, we observed decreased expression of Id1 as well as the E2-responsive gen…
Progenitor death drives retinal dysplasia and neuronal degeneration in a mouse model of Atrip-Seckel syndrome
2020
ABSTRACT Seckel syndrome is a type of microcephalic primordial dwarfism (MPD) that is characterized by growth retardation and neurodevelopmental defects, including reports of retinopathy. Mutations in key mediators of the replication stress response, the mutually dependent partners ATR and ATRIP, are among the known causes of Seckel syndrome. However, it remains unclear how their deficiency disrupts the development and function of the central nervous system (CNS). Here, we investigated the cellular and molecular consequences of ATRIP deficiency in different cell populations of the developing murine neural retina. We discovered that conditional inactivation of Atrip in photoreceptor neurons …
Current advancement in immunosensing of p53 tumor suppressor protein based on nanomaterials: Analytical approach
2017
Abstract The utility of detection of p53 in tomorrow's personalized health care field will mean early and accurate diagnosis of many types of cancers. This review is meant to provide an overview of the various types of immunosensors and immunoassay have been developed for determination of p53, along with significant advances over the last several years in related technologies. In addition, this review described: • Most frequently applied principles in immunoassay/immunosensing of p53. • The aspects of fabrication in the perspective of immunoassay/immunosensing applications. • The potential of various electrochemical, electrochemiluminescence immunosensors for the determination of p53 within…
Identification and characterization of a monoclonal antibody to the membrane fatty acid binding protein
1992
A monoclonal antibody to the rat liver membrane fatty acid binding protein (MFABP) was prepared by immunizing mice with purified MFABP isolated from solubilized rat liver plasma membrane proteins by oleate-agarose affinity chromatography technique. The monoclonal antibody K15/6 identified a single 40 kDa protein in rat liver plasma membranes with pI values of 8.5, 8.8 and 9.0, which is identical to the authentic MFABP, but clearly distinct from rat mitochondrial GOT. The antibody K15/6 selectively inhibited cellular influx as well as membrane binding of fatty acids, but not of cholesterol or vitamin E. The same antibody was used in immunofluorescence, ELISA and Western blot analysis to dete…