RESUMEN
Interactions between epithelial cells and the extracellular matrix are central to tissue homeostasis and have a dynamic role in tissue remodeling and repair. Regulation of these pathways is balanced by positive and negative feedback elements, many of which have been implicated in the pathways of malignant progression. We have used differential display to identify genes that are up-regulated in normal human urothelial cells in response to exposure to extracellular matrix proteins (Matrigel) in vitro. This approach has identified genes that have key roles in cell-cell and cell-matrix interactions and that have been implicated in the progression of carcinomas of urothelial or other epithelial cell origins. One confirmed but unknown differentially expressed sequence was used to isolate a full-length gene, MIG-C4, from a human urothelial cDNA library. This gene was found to encode a novel urokinase plasminogen-activator receptor-like member of the Ly-6 family of glycosyl-phosphatidylinositol-anchored glycoproteins, and was identified as the human homologue of the rat metastasis-associated C4.4A gene. By in situ hybridization, MIG-C4 was expressed variably in normal urothelium and intensely in the tumor component of some noninvasive superficial lesions and in invasive and metastatic urothelial cancers. Thus, our approach has identified previously nonimplicated gene products involved in normal urothelium-matrix interactions that could be tumor-invasion or suppressor-gene targets in the development of invasive and metastatic tumor phenotypes.
Asunto(s)
Carcinoma de Células Transicionales/genética , Matriz Extracelular/fisiología , Pelvis Renal/fisiología , Uréter/fisiología , Neoplasias Urológicas/genética , Secuencia de Aminoácidos , Animales , Carcinoma de Células Transicionales/metabolismo , Comunicación Celular/genética , Comunicación Celular/fisiología , Colágeno , ADN Complementario/genética , ADN Complementario/aislamiento & purificación , Combinación de Medicamentos , Matriz Extracelular/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Hibridación in Situ , Pelvis Renal/citología , Pelvis Renal/metabolismo , Laminina , Datos de Secuencia Molecular , Proteoglicanos , Ratas , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Homología de Secuencia de Aminoácido , Células Tumorales Cultivadas , Uréter/citología , Uréter/metabolismo , Neoplasias Urológicas/metabolismoAsunto(s)
Antibacterianos/uso terapéutico , Infecciones por Chlamydia/tratamiento farmacológico , Chlamydophila pneumoniae/patogenicidad , Ensayos Clínicos como Asunto/métodos , Enfermedad Coronaria/prevención & control , Proyectos de Investigación , Antibacterianos/efectos adversos , Biomarcadores/sangre , Infecciones por Chlamydia/sangre , Infecciones por Chlamydia/complicaciones , Enfermedad Coronaria/sangre , Enfermedad Coronaria/microbiología , Humanos , Estudios Multicéntricos como Asunto , Selección de Paciente , Proyectos Piloto , Factores de TiempoAsunto(s)
Bloqueo Cardíaco/etiología , Lesiones Cardíacas/complicaciones , Infarto del Miocardio/etiología , Heridas no Penetrantes/complicaciones , Angiografía Coronaria , Ecocardiografía , Electrocardiografía , Bloqueo Cardíaco/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnósticoAsunto(s)
Proteínas Bacterianas/biosíntesis , Escherichia coli/genética , Plásmidos , Mapeo Cromosómico , Cromosomas Bacterianos , Enzimas de Restricción del ADN/metabolismo , Elementos Transponibles de ADN , ADN Bacteriano , Desoxirribonucleasa EcoRI , Electroforesis en Gel de Poliacrilamida , Genes Bacterianos , Genes Reguladores , Biosíntesis de Proteínas , Recombinación Genética , Transcripción GenéticaRESUMEN
Fla-, Pil-mutants of Escherichia coli K-12 were found to have decreased transfer efficiency of F-like resistance plasmids as compared to the parent strains. This was accompanied by decreased production of conjugation pili and decreased resistance level to some, but not all, of the antibiotics to which resistance was conferred. There was no reduction in pilus production or transfer efficiency in any of the mutants when the plasmid was F'gal. This host-mediated influence on conjugation pilus production is discussed with reference to a possible loss of cell envelope integrity which causes the simultaneous loss of all cellular appendage structures.
