ABSTRACT
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.
Subject(s)
Carcinoma, Transitional Cell/genetics , Extracellular Matrix/physiology , Kidney Pelvis/physiology , Ureter/physiology , Urologic Neoplasms/genetics , Amino Acid Sequence , Animals , Carcinoma, Transitional Cell/metabolism , Cell Communication/genetics , Cell Communication/physiology , Collagen , DNA, Complementary/genetics , DNA, Complementary/isolation & purification , Drug Combinations , Extracellular Matrix/metabolism , Gene Expression Profiling , Gene Expression Regulation , Gene Expression Regulation, Neoplastic , Humans , In Situ Hybridization , Kidney Pelvis/cytology , Kidney Pelvis/metabolism , Laminin , Molecular Sequence Data , Proteoglycans , Rats , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Amino Acid , Tumor Cells, Cultured , Ureter/cytology , Ureter/metabolism , Urologic Neoplasms/metabolismSubject(s)
Anti-Bacterial Agents/therapeutic use , Chlamydia Infections/drug therapy , Chlamydophila pneumoniae/pathogenicity , Clinical Trials as Topic/methods , Coronary Disease/prevention & control , Research Design , Anti-Bacterial Agents/adverse effects , Biomarkers/blood , Chlamydia Infections/blood , Chlamydia Infections/complications , Coronary Disease/blood , Coronary Disease/microbiology , Humans , Multicenter Studies as Topic , Patient Selection , Pilot Projects , Time FactorsSubject(s)
Alcoholism/therapy , Medicine , Specialization , Substance-Related Disorders/therapy , Humans , United StatesSubject(s)
Alcoholism/rehabilitation , Substance-Related Disorders/rehabilitation , Family Practice , Humans , OhioSubject(s)
Physician Impairment , Physician's Role , Role , Societies, Medical , Substance-Related Disorders/therapy , Humans , OhioSubject(s)
Bacterial Proteins/biosynthesis , Escherichia coli/genetics , Plasmids , Chromosome Mapping , Chromosomes, Bacterial , DNA Restriction Enzymes/metabolism , DNA Transposable Elements , DNA, Bacterial , Deoxyribonuclease EcoRI , Electrophoresis, Polyacrylamide Gel , Genes, Bacterial , Genes, Regulator , Protein Biosynthesis , Recombination, Genetic , Transcription, GeneticABSTRACT
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.