Search results for "oncogen"
showing 10 items of 1031 documents
Analysis of p53 and mdm2 proteins in malignant fibrous histiocytoma in absence of gene alteration: prognostic significance.
2000
TP53 and MDM2 genes and their protein expression were evaluated in frozen and paraffin-embedded tissue from 27 patients with malignant fibrous histiocytoma to elucidate the relationship between them, their implication in tumor progression mechanisms and their possible diagnostic-prognostic value in malignant fibrous histiocytoma. Single-strand conformation polymorphism analysis and direct sequencing of polymerase chain reaction-amplified DNA were used to establish two TP53 mutations (7.4%): a point mutation and a 63-bp duplication. Amplification of the MDM2 gene was observed in two tumors (7.4%) by means of Southern-blot analysis, one of them also carrying the TP53 point mutation. Immunohis…
Analysis of the p53 and MDM-2 gene in acute myeloid leukemia
1996
The MDM-2 (murine double minute 2) gene codes for a cellular protein that can bind to the p53 tumor suppressor gene product, thereby functioning as a negative regulator of p53. In order to define the role of the MDM-2 gene in the pathogenesis of human acute myeloid leukemia, the expression and the sequence of the MDM-2 gene were examined in samples of bone marrow and/or peripheral mononuclear cells of 38 patients by using immunostaining, polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing. Immunohistochemical staining detected a weak accumulation of the MDM-2 protein in AML patients of FAB classification M4 and M5. RT-PCR analysis revealed a heterogeneou…
Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis
2004
The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation–deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2family proteins that share only the third Bcl-2homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentra…
Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor.
2007
Recently, we identified htid-1, the human counterpart of the Drosophila tumor suppressor gene lethal(2)tumorous imaginal discs [l(2)tid], as a direct molecular ligand of the adenomatous polyposis coli (APC) tumor suppressor. The gene encodes three cytosolic (Tid50, Tid48 and Tid46) and three mitochondrial (Tid43, Tid40 and Tid38) proteins. In the colorectal epithelium the cytosolic forms hTid50/hTid48 interact under physiological conditions with the N-terminal region of APC. This complex which associates with additional proteins such as Hsp70, Hsc70, Actin, Dvl and Axin defines a novel physiological state of APC unrelated to beta-catenin degradation. Here we show that the expression of the …
Caracterización del supresor tumoral DRO1 y su regulación transcripcional por AIB1
2012
El cáncer es una enfermedad de gran importancia puesto que es una de las principales causas de muerte en el mundo. Los principales factores de riesgo para el desarrollo de la enfermedad son la edad o el estilo de vida que promueve un índice de masa corporal elevado, ingesta reducida de frutas y verduras, falta de actividad física, consumo de tabaco y consumo de alcohol. Sin embargo, en la aparición del cáncer también se encuentran implicados otros factores como son la predisposición genética o la presencia de enfermedades como la obesidad o ciertos virus que pueden influir en el desarrollo del cáncer. La causa de esta enfermedad es la acumulación progresiva de alteraciones genéticas que con…
Human Papilloma Virus-Dependent HMGA1 Expression Is a Relevant Step in Cervical Carcinogenesis
2008
HMGA1 is a member of a small family of architectural transcription factors involved in the coordinate assembly of multiprotein complexes referred to as enhanceosomes. In addition to their role in cell proliferation, differentiation, and development, high-mobility group proteins of the A type (HMGA) family members behave as transforming protoncogenes either in vitro or in animal models. Recent reports indicated that HMGA1 might counteract p53 pathway and provided an interesting hint on the mechanisms determining HMGA's transforming potential. HMGA1 expression is deregulated in a very large array of human tumors, including cervical cancer, but very limited information is available on the mole…
Liver specific overexpression of platelet-derived growth factor-B accelerates liver cancer development in chemically induced liver carcinogenesis
2010
A genetic basis of hepatocellular carcinoma (HCC) has been well-established and major signaling pathways, such as p53, Wnt-signaling, transforming growth factor-β (TGF-β) and Ras pathways, have been identified to be essential to HCC development. Lately, the family of platelet-derived growth factors (PDGFs) has shifted to the center of interest. We have reported on spontaneously developing liver fibrosis in PDGF-B transgenic mice. Since HCC rarely occurs in healthy liver, but dramatically increases at the cirrhosis stage of which liver fibrosis is a preliminary stage, we investigated liver cancer development in chemically induced liver carcinogenesis in these mice. HCC induction was performe…
Human Fetal Aorta Contains Vascular Progenitor Cells Capable of Inducing Vasculogenesis, Angiogenesis, and Myogenesis in Vitro and in a Murine Model …
2007
Vasculogenesis, the formation of blood vessels in embryonic or fetal tissue mediated by immature vascular cells (ie, angioblasts), is poorly understood. We report the identification of a population of vascular progenitor cells (hVPCs) in the human fetal aorta composed of undifferentiated mesenchymal cells that coexpress endothelial and myogenic markers. Under culture conditions that promoted cell differentiation, hVPCs gave rise to a mixed population of mature endothelial and mural cells when progenitor cells were stimulated with vascular endothelial growth factor-A or platelet-derived growth factor-betabeta. hVPCs grew as nonadherent cells and, when embedded in a three-dimensional collagen…
Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascul…
2012
Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), …
Synthesis of Combretastatin A-4 and 3′-Aminocombretastatin A-4 derivatives with Aminoacid Containing Pendants and Study of their Interaction with Tub…
2020
Natural product combretastatin A-4 (CA-4) and its nitrogenated analogue 3&prime