Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Microvasc Res ; 60(2): 91-103, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10964583

RESUMO

The mouse Notch4 gene is expressed specifically in endothelial cells. Notch4/int-3, a truncated form of Notch4, acts as a constitutive activated Notch receptor. We used rat brain microvessel endothelial cells (RBE4) to study the role of Notch4 and Jagged-1 in endothelial cell differentiation. Both Notch4/int-3 and Jagged-1 were able to induce microvessel-like structures with morphological and biochemical properties similar to brain endothelial microvessels. Ectopic expression of full-length Notch4 did not effect RBE4 cells. Activation of the Notch signal transduction pathway was measured by the induction of endogenous Notch4 and Jagged-1 genes and of Jagged-1 proteins. The observed morphological changes to RBE4 cells correlated with endogenous Notch4 and Jagged-1 gene activation. Our observations demonstrate that Notch signaling can promote endothelial cell differentiation and morphogenesis.


Assuntos
Capilares/citologia , Capilares/fisiologia , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Proteínas/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Receptores de Superfície Celular , Animais , Encéfalo/irrigação sanguínea , Proteínas de Ligação ao Cálcio , Diferenciação Celular/fisiologia , Circulação Cerebrovascular , Peptídeos e Proteínas de Sinalização Intercelular , Proteína Jagged-1 , Proteínas de Membrana , Camundongos , Morfogênese/fisiologia , Neovascularização Fisiológica , Ratos , Receptor Notch4 , Receptores Notch , Proteínas Serrate-Jagged
2.
Genes Dev ; 14(11): 1343-52, 2000 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-10837027

RESUMO

The Notch gene family encodes large transmembrane receptors that are components of an evolutionarily conserved intercellular signaling mechanism. To assess the role of the Notch4 gene, we generated Notch4-deficient mice by gene targeting. Embryos homozygous for this mutation developed normally, and homozygous mutant adults were viable and fertile. However, the Notch4 mutation displayed genetic interactions with a targeted mutation of the related Notch1 gene. Embryos homozygous for mutations of both the Notch4 and Notch1 genes often displayed a more severe phenotype than Notch1 homozygous mutant embryos. Both Notch1 mutant and Notch1/Notch4 double mutant embryos displayed severe defects in angiogenic vascular remodeling. Analysis of the expression patterns of genes encoding ligands for Notch family receptors indicated that only the Dll4 gene is expressed in a pattern consistent with that expected for a gene encoding a ligand for the Notch1 and Notch4 receptors in the early embryonic vasculature. These results reveal an essential role for the Notch signaling pathway in regulating embryonic vascular morphogenesis and remodeling, and indicate that whereas the Notch4 gene is not essential during embryonic development, the Notch4 and Notch1 genes have partially overlapping roles during embryogenesis in mice.


Assuntos
Vasos Sanguíneos/embriologia , Proteínas Proto-Oncogênicas/fisiologia , Receptores de Superfície Celular , Fatores de Transcrição , Fatores Etários , Animais , Embrião de Mamíferos/metabolismo , Homozigoto , Hibridização In Situ , Peptídeos e Proteínas de Sinalização Intracelular , Ligantes , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Morfogênese , Mutagênese , Neovascularização Fisiológica/genética , Fenótipo , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/biossíntese , Receptor Notch1 , Receptor Notch4 , Receptores de Fatores de Crescimento/biossíntese , Receptores Notch , Receptores de Fatores de Crescimento do Endotélio Vascular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais
3.
J Biol Chem ; 271(48): 30366-74, 1996 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-8939998

RESUMO

RhoB is a small GTP-binding protein highly homologous to the RhoA protein. While RhoA is known to regulate the assembly of focal adhesions and stress fibers in response to growth factors, the function of RhoB remains unknown. We have reported that the transient expression of the endogenous RhoB protein is regulated during the cell cycle, contrasting with the permanent RhoA protein expression (). Using the yeast two-hybrid system to characterize proteins interacting with RhoB, we identified a new mouse Rho GDP dissociation inhibitor, referenced as RhoGDI-3. The NH2-terminal alpha helix of RhoGDI-3 is strongly amphipatic and differs thus from that found in previously described bovine, human, and yeast RhoGDI proteins and mouse and human D4/Ly-GDIs. Contrary to the cytosolic localization of all known GDI proteins, acting on Rab or Rho, RhoGDI-3 is associated to a Triton X-100-insoluble membranous or cytoskeletal subcellular fraction. In the two-hybrid system, RhoGDI-3 interacts specifically with GDP- and GTP-bound forms of post-translationally processed RhoB and RhoG proteins, both of which show a growth-regulated expression in mammalian cells. No interaction is found with RhoA, RhoC, or Rac1 proteins. We show that GDI-3 is able to inhibit GDP/GTP exchange of RhoB and to release GDP-bound but not GTP-bound RhoB from cell membranes.


Assuntos
GTP Fosfo-Hidrolases , Proteínas de Ligação ao GTP/metabolismo , Inibidores de Dissociação do Nucleotídeo Guanina , Proteínas de Membrana/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Cromossomos Humanos Par 16 , Clonagem Molecular , Proteínas de Ligação ao GTP/genética , Guanosina Difosfato/metabolismo , Guanosina Trifosfato/metabolismo , Células HeLa , Humanos , Membranas/metabolismo , Camundongos , Dados de Sequência Molecular , Ligação Proteica , Estrutura Secundária de Proteína , RNA Mensageiro/genética , Saccharomyces cerevisiae , Alinhamento de Sequência , Distribuição Tecidual , Proteínas rho de Ligação ao GTP , Inibidor alfa de Dissociação do Nucleotídeo Guanina rho , Inibidor gama de Dissociação do Nucleotídeo Guanina rho , Inibidores da Dissociação do Nucleotídeo Guanina rho-Específico , Proteína rhoB de Ligação ao GTP
4.
Oncogene ; 10(10): 1935-45, 1995 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-7539118

RESUMO

The immediate-early gene rhoB codes for a small GTP-binding protein highly homologous to the RhoA protein. While RhoA is known to regulate the assembly of focal adhesions and stress fibers in response to growth factors, the function of RhoB remains unknown. In a first attempt to elucidate its function, we examined the variation of the RhoB protein expression in response to induction of its mRNA. We report here that RhoB is an unstable protein rapidly and transiently induced by growth factors in PC12 and HeLa cells. Moreover, RhoB protein accumulation is periodic through the cell cycle. First detected at the G1/S phase transition, the level of the RhoB protein is maximal during the S phase and declines at the S/G2-M transition. This timing suggests that RhoB plays a role in the G1/S phase transition and/or in the S phase of the cell cycle. We also confirm here a vesicular and perinuclear localization of the endogenous RhoB protein induced by growth factors.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Proteínas de Membrana/metabolismo , Ciclo Celular , Linhagem Celular , AMP Cíclico/farmacologia , Proteínas de Ligação ao GTP/análise , Células HeLa/citologia , Células HeLa/metabolismo , Humanos , Proteínas de Membrana/análise , Fatores de Crescimento Neural/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , RNA/metabolismo , Proteína rhoB de Ligação ao GTP
5.
Can J Hosp Pharm ; 48(2): 90-7, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10142843

RESUMO

Granulocyte Colony-Stimulating Factor or G-CSF (NEUPOGEN) was approved for use in France in November 1991 for prevention of chemotherapy-induced neutropenia. This retrospective study was conducted at Saint-Louis Hospital, Paris, France, from November 1991 to March 1993 with a more detailed analysis of patient profiles for courses ordered between November 1991 and December 1992. Data were collected on standardized G-CSF-treatment summary forms. The purpose of the study was to define, in clinical terms, the patients treated by G-CSF to determine the average cost per course of therapy and its impact on the hospital pharmacy budget. From November 1991 to December 1992 data from 307 patient profiles were collected and analyzed. The subcutaneous route was the preferred route and only 16.6% of courses were administered intravenously. 45.6% of patients received a single course, 24.3% received two courses, and 30.1% received more than two courses. Each patient completed an average of 2.3 courses at an average cost per course of $2,000.00 (Canadian dollars). During March 1993, 50% of vials dispensed were administered to outpatients. During the 14-month period, an average of 613.8 vials were dispensed per month corresponding to an average monthly expenditure of $104,000.00 (Canadian dollars). In the first 12 months following the commercial availability of G-CSF, G-CSF expenditures accounted for 8% of the pharmacy budget.


Assuntos
Custos de Medicamentos/estatística & dados numéricos , Serviço Hospitalar de Oncologia/economia , Serviço de Farmácia Hospitalar/economia , Receptores de Fator Estimulador de Colônias de Granulócitos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Coleta de Dados , Revisão de Uso de Medicamentos/estatística & dados numéricos , Controle de Formulários e Registros , França , Hospitais com mais de 500 Leitos , Custos Hospitalares/estatística & dados numéricos , Hospitais Universitários/economia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Int J Cancer ; 59(3): 408-15, 1994 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-7927950

RESUMO

The mRNA levels of the ras-related human rhoA, rhoB and rhoC genes were studied in human breast-cancer cell lines (HBCal), and in normal and immortalized mammary epithelial cells (HMEC) by Northern blot analysis and in situ hybridization. In contrast to the ubiquitous rhoA and rhoC gene expression, dramatic variations in the mRNA level of the rhoB gene were evidenced. The rhoB mRNA level appeared to be inversely correlated to the amounts of the epidermal-growth-factor(EGF) receptors in these cells. The rhoB transcripts were detected at high levels in ZR75-1, MCF7, HSL 53, HSL 59, HSL 90, T47D and SKBR3 HBCal, at hardly detectable levels in BT 20, MDA-MB 231 and H466B HBCal and at intermediate levels in normal and immortalized breast epithelial cells. Rapid and transient induction of the rhoB transcription was observed after EGF treatment in serum-deprived MDA-MB231, T47D and immortalized epithelial cells. In contrast, no modulation of rhoB expression by EGF could be objectified in the MCF7 and ZR75-1 cell lines. Yet a normal function of EGF receptors was evidenced, since the immediate early gene c-fos was rapidly induced, suggesting a constitutive expression of rhoB in these cell lines bypassing the regulation by EGF. In human mammary epithelial cells, rhoB mRNA is rapidly and transiently induced with EGF concentrations known to stimulate cell proliferation. This suggests that the rhoB product might be involved in a cascade that initiates or promotes cell proliferation, and plays an important role in EGF-stimulated growth of breast normal and cancer cells.


Assuntos
Neoplasias da Mama/metabolismo , Fator de Crescimento Epidérmico/farmacologia , GTP Fosfo-Hidrolases/biossíntese , Proteínas de Ligação ao GTP/biossíntese , Regulação Neoplásica da Expressão Gênica/imunologia , Proteínas de Membrana/biossíntese , Northern Blotting , Feminino , GTP Fosfo-Hidrolases/genética , Proteínas de Ligação ao GTP/genética , Humanos , Hibridização In Situ , Proteínas de Membrana/genética , Sondas de Ácido Nucleico , Proteínas Proto-Oncogênicas c-fos/biossíntese , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Células Tumorais Cultivadas , Proteína rhoB de Ligação ao GTP
7.
Eur J Cancer ; 30A(5): 670-4, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8080685

RESUMO

ras oncoproteins and ras-related proteins constitute a large family of the small GTP-binding protein family. The rab branch of the ras superfamily is involved in the intracellular transport along the secretory and endocytic pathway in eukaryotic cells. We here demonstrate that a member of the rab branch, the rab2 protein, is frequently overexpressed in peripheral blood mononuclear cells from patients with solid neoplasms. Moreover, this expression is shown to be greatly modified during the course of therapy. Our results provide strong evidence for the implication of a small GTP-binding protein in immunological events associated with neoplastic diseases. The precise cellular population involved as well as the potential prognostic value of this process remains to be determined.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Guanosina Trifosfato/metabolismo , Leucócitos Mononucleares/química , Proteínas de Neoplasias/sangue , Neoplasias/sangue , Antineoplásicos/uso terapêutico , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Interleucina-2/uso terapêutico , Masculino , Estudos Prospectivos , Neoplasias Urogenitais/sangue , Neoplasias Urogenitais/terapia , Proteína rab2 de Ligação ao GTP
8.
Leukemia ; 7(4): 601-8, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8096558

RESUMO

The Rab branch of the Ras-related GTP/GDP-binding proteins currently includes at least 25 related members which are involved in the intracellular vesicular transport along the secretory and endocytic pathways in eukaryotic cells. The overexpression of the Rab2 protein in peripheral mononuclear cells is demonstrated from 13 out of 17 patients exhibiting a Sézary syndrome. Moreover, this phenomenon is detectable in other lymphoid and myeloid malignancies. Several lines of evidence are shown suggesting that the Rab2 overexpression can be related not to leukemic cells but to a subset of peripheral lymphocytes with a CD2+ phenotype. Our results provides strong evidence for the implication of a small GDP/GTP-binding protein in immunological events associated with neoplastic states. The precise cellular population involved in this process remains to be determined.


Assuntos
Antígenos de Diferenciação de Linfócitos T/biossíntese , Proteínas de Ligação ao GTP/biossíntese , Linfócitos/imunologia , Receptores Imunológicos/biossíntese , Síndrome de Sézary/sangue , Antígenos CD2 , Humanos , Mapeamento por Restrição , Formação de Roseta , Proteína rab2 de Ligação ao GTP
9.
Nouv Rev Fr Hematol (1978) ; 35(1): 41-4, 1993 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8511040

RESUMO

The Rab branch of the Ras-related guanine nucleotide (GTP/GDP)-binding proteins currently includes at least thirty related members which are involved in the intracellular vesicular transport along the secretory and endocytic pathways in eukaryotic cells. We have demonstrated the overexpression of the Rab2 protein in peripheral blood mononuclear cells from patients exhibiting Sézary syndromes and other lymphoid and myeloid malignancies. Several lines of evidence suggest that the Rab2 overexpression can be related not to leukemic cells but to a subset of peripheral lymphocytes with a CD2+ phenotype. Our results provide strong evidences for the implication of a small GDP/GTP binding protein in immunological events associated with neoplastic states. The precise cellular population involved in this process remains to be determined.


Assuntos
Proteínas de Ligação ao GTP/fisiologia , Síndrome de Sézary/imunologia , Neoplasias Cutâneas/imunologia , Regulação Neoplásica da Expressão Gênica , Genes ras , Humanos , Leucócitos Mononucleares/metabolismo , Família Multigênica , Proteínas de Neoplasias/fisiologia , Síndrome de Sézary/genética , Neoplasias Cutâneas/genética , Proteína rab2 de Ligação ao GTP
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...