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At least 73 records · Page 4Linked to original sources
PubMed2000

DMBT1 encodes a protein involved in the immune defense and in epithelial differentiation and is highly unstable in cancer.

The gene deleted in malignant brain tumors 1 (DMBT1) has been proposed as a candidate tumor suppressor for brain, gastrointestinal, and lung cancer. It codes for a protein of unknown function belonging to the superfamily of scavenger receptor cysteine-rich proteins. We aimed at getting insights into the functions of DMBT1 by expression analyses and studies with a monoclonal antibody against the protein. The DMBT1 mRNA is expressed throughout the immune system, and Western blot studies demonstrated that isoforms of DMBT1 are identical to the collectin-binding protein gp-340, a glycoprotein that is involved in the respiratory immune defense. Immunohistochemical analyses revealed that DMBT1 is produced by both tumor-associated macrophages and tumor cells and that it is deregulated in glioblastoma multiforme in comparison to normal brain tissue. Our data further suggest that the proteins CRP-ductin and hensin, both of which have been implicated in epithelial differentiation, are the DMBT1 orthologs in mice and rabbits, respectively. These findings and the spatial and temporal distribution of DMBT1 in fetal and adult epithelia suggest that DMBT1 further plays a role in epithelial development. Rearrangements of DMBT1 were found in 16 of 18 tumor cell lines, and hemizygous deletions were observed in a subset of normal individuals, indicating that the alterations in tumors may be a result of both pre-existing deletions uncovered by a loss of heterozygosity and secondary changes acquired during tumorigenesis. Thus, DMBT1 is a gene that is highly unstable in cancer and encodes for a protein with at least two different functions, one in the immune defense and a second one in epithelial differentiation.

Agglutinins↗
PubMed2003

Human papillomavirus type 31 E5 protein supports cell cycle progression and activates late viral functions upon epithelial differentiation.

The function of the E5 protein of human papillomaviruses (HPV) is not well characterized, and controversies exist about its role in the viral life cycle. To determine the function of E5 within the life cycle of HPV type 31 (HPV31) we first constructed HPV31 mutant genomes that contained an altered AUG initiation codon or stop codons in E5. Cell lines were established which harbored transfected wild-type or E5 mutant HPV31 genomes. These cell lines all maintained episomal copies of HPV31 and revealed similar phenotypes with respect to growth rate, early gene expression, and viral copy number in undifferentiated monolayer cultures. Following epithelial differentiation, genome amplification and differentiation-dependent late gene expression were observed in mutant cell lines, but at a rate significantly reduced from that observed in cells containing the wild-type genomes. Organotypic raft cultures indicated that E5 does not effect the expression of differentiation markers but does reduce expression of late viral proteins. Western analysis and immunofluorescence staining for cyclins during epithelial differentiation revealed a decreased expression of cyclin A and B in E5 mutant cells compared to HPV wild-type cells. Using a replating assay, a significant reduction in colony-forming ability was detected in the absence of E5 expression when cells containing wild-type or E5 mutant HPV genomes were allowed to proliferate following 24 h in suspension-induced differentiation. This suggests that HPV E5 modifies the differentiation-induced cell cycle exit and supports the ability of HPV31-positive keratinocytes to retain proliferative competence. In these studies, E5 was found to have little effect on the levels of the epidermal growth factor receptor (EGFR) or on its phosphorylation status. This indicates that EGFR is not a target of E5 action. Our results propose a role for high risk HPV E5 in modulation of late viral functions through activation of proliferative capacity in differentiated cells. We suspect that the primary target of E5 is a membrane protein or receptor that then acts to alter the levels or activities of cell cycle regulators.

Cell Cycle↗
PubMed2002

Evidence for a plasma membrane-mediated permeability barrier to Tat basic domain in well-differentiated epithelial cells: lack of correlation with heparan sulfate.

Membrane permeation peptides, such as Tat basic domain, have emerged as useful membrane transduction agents with potential utility in therapeutic delivery and diagnostic imaging. While generally thought to universally permeate all cells by a nonselective process, the mechanism of membrane transduction remains poorly characterized. To examine vectorial transport properties of Tat basic domain in well-differentiated epithelial cells possessing tight junctions, L and D stereoisomers of Tat(48-57) peptide conjugates labeled with (99m)Tc were quantitatively analyzed in confluent monolayers of MDCK renal epithelial and CaCo-2 colonic carcinoma cells grown in transwell configurations. In both cell lines, vectorial transepithelial apparent permeability coefficients (P(app)) for L- and D-[(99m)Tc]Tat-peptides ranged from 30 to 70 nm/s, comparable to values for the macromolecular impermeant marker inulin in both apical-to-basolateral and basolateral-to-apical directions, but 100-fold less than the P(app) values for propranolol, a highly permeable control compound. Upon direct instillation of [(99m)Tc]Tat-peptide into the urinary bladder of living rats in vivo, no transepithelial permeation into other tissues was identified. Furthermore, MDCK and CaCo-2 cells showed a complete lack of intracellular accumulation of fluorescein conjugated Tat-peptide. However, translocation into cells was induced by treatment with plasma membrane permeabilizing agents such as digitonin and acetone/methanol, while cholesterol depletion with beta-methyl-cyclodextrin and metabolic inhibition with CCCP or 4 degrees C showed no effect. By contrast, in Hela and KB 3-1 cells, epithelial lines that do not form tight junctions in monolayer culture, baseline cytoplasmic and nucleolar accumulation was readily observed. Because all four cell lines expressed heparan sulfate proteoglycans, putative receptors for Tat basic peptides, we found no correlation between heparan sulfate and the permeation barrier observed in MDCK and CaCo-2 cells. The unanticipated presence of a permeation barrier to Tat-peptides in well-differentiated epithelial cells suggests the existence of cell-specific mechanisms for mediated translocation of these permeation peptides.

Administration, Intravesical↗
PubMedDate not supplied

The long-term effect of clomiphene citrate on vaginal epithelial differentiation in the mouse.

Clomiphene citrate, administered to the neonatal mouse during cervicovaginal epithelial differentiation, is associated with subsequent adenosis. Similar lack of neonatal transformation of columnar to squamous epithelium occurs after diethylstilbestrol. Mouse neonatally exposed to diethylstilbestrol have a high incidence of reproductive tract tumors in later life. In this study Balb/c neonates were exposed to clomiphene citrate, maintained with controls, and killed at 52, 56, and 60 weeks. Cervicovaginal histology was studied by light microscopy. In all control animals only mature squamous epithelium was seen (44/44). After clomiphene citrate, at 52 weeks, 3/10 animals had other than mature squamous epithelium identified. One of these genital tracts contained adenosis. At 56 weeks only mature squamous epithelium was seen (11/11), and at 60 weeks immature squamous epithelium was identified in 1 of 10 animals. In no study animal (0/31) was there any evidence of tumor development. This differs from the high incidence of reproductive tract tumor seen in the mouse after neonatal diethylstilbestrol exposure.

Animals↗
PubMedDate not supplied

Eyelid fusion and epithelial differentiation at the ocular surface during mouse embryonic development.

PURPOSE: To investigate epithelial differentiation at the ocular surface of the developing mouse eye by examining temporal and spatial changes in the expression of specific keratins. METHODS: Ocular tissues, including the entire eyeball, conjunctiva, and eyelid, of mouse embryos at embryonic day (E) 12.5 to E18.5 as well as of adult mice were examined by hematoxylin-eosin staining and by immunohistochemistry with antibodies to keratins K4, K10, K12, and K14. RESULTS: Hematoxylin-eosin staining revealed that eyelid fusion occurred at E17.5. Keratin immunohistochemistry demonstrated that: (1) K4 was expressed before K12, which in turn was expressed before K10; (2) expression of K4, K12, and K14 was spatially heterogeneous in the epithelia of the eyelid invaginations before eyelid fusion, but thereafter was continuous and homogeneous in the entire conjunctival epithelium, corneal epithelium, and basal cell layer of the surface epithelia, respectively; and (3) K10 immunoreactivity was not detected before eyelid fusion but was apparent in the epidermis of the eyelid thereafter. CONCLUSIONS: Eyelid fusion is a critical period for differentiation of the ocular surface ectoderm into the epithelia of the conjunctiva, cornea, and eyelid skin. The conjunctival epithelium differentiates before the corneal epithelium, which in turn differentiates before the eyelid epidermis.

Animals↗
PubMed1997

Epithelial differentiation in Drosophila.

Our understanding of epithelial development in Drosophila has been greatly improved in recent years. Two key regulators of epithelial polarity, Crumbs and DE-cadherin, have been studied at the genetic and molecular levels and a number of additional genes are being analyzed that contribute to the differentiation of epithelial cell structure. Epithelial architecture has a profound influence on morphogenetic movements, patterning and cell-type determination. The combination of embryological and genetic/molecular tools in Drosophila will help us to elucidate the complex events that determine epithelial cell structure and how they relate to morphogenesis and other developmental processes.

Animals↗
PubMed1988

Cooperation between the polyomavirus middle-T-antigen gene and the human c-myc oncogene in a rat thyroid epithelial differentiated cell line: model of in vitro progression.

Two rat thyroid epithelial differentiated cell lines, PC Cl 3 and PC myc, were infected with the polyoma murine leukemia virus (PyMLV) carrying the Middle-T-antigen gene of polyomavirus. After infection, both cell lines acquired the typical markers of neoplastic transformation; however, the PC myc cells showed a greater malignant phenotype. Furthermore, the thyroid differentiated functions were completely suppressed in PC myc cells transformed by PyMLV, whereas they were, at least partially, retained in PC Cl 3 cells transformed by PyMLV, and in particular, thyroglobulin synthesis and secretion were not affected at all. Since no differences in the expression of the middle-T-antigen gene were observed in the two PyMLV-transformed cell lines, the different properties shown by these two infected cell lines must be ascribed to the expression of the c-myc oncogene.

Animals↗
PubMed1987

Lack of biological activity of physiological metabolites of all-trans-retinoic acid on vaginal epithelial differentiation.

It has been of interest to determine whether the metabolites of physiological doses of retinoic acid represent active forms of vitamin A. Previous work (Biochem. J. 206, 33-41, 1982) studied the metabolites produced from 2-micrograms doses of all-trans-retinoic acid in the vitamin A-deficient rat. Four major metabolites common to all of the tissues studied were discovered. In the present work, three of these metabolites are isolated from vitamin A-deficient rats given physiological doses (5 micrograms) of all-trans-retinoic acid and from vitamin A-sufficient rats given high doses (1 mg) of all-trans-retinoic acid. Cochromatography on anion-exchange and reverse-phase high-performance liquid chromatography showed that metabolites resulting from high doses of retinoic acid contained the metabolites generated from physiological doses of retinoic acid. Quantities of these metabolites were isolated, purified, and tested for their epithelial-differentiating activity in the vitamin A-deficient rat vagina. The metabolites were inactive at all dose levels tested. These metabolites have less than 10% the biological activity of all-trans-retinoic acid. Therefore, these metabolites appear to be products of the inactivation of all-trans-retinoic acid. Based upon these and previous data, it seems likely that all-trans-retinoic acid or its beta-glucuronide derivative is the most likely active form of vitamin A in the maintenance of normal epithelial differentiation.

Animals↗
PubMed1986

Developing differentiated epithelial cell cultures: airway epithelial cells.

Recent progress in cell culture enables us to grow and to maintain differentiated epithelial cells in a serum-free defined culture environment. Such an epithelial cell culture system free from interference by other nonepithelial cell types should be used widely in studies related to toxicology, carcinogenesis, and disease-related problems. This approach will lead to a better understanding of pathological changes indicated in the injured epithelial layer. The gap of information existing between in vivo and in vitro can be bridged together by this simple epithelial cell culture system by carefully analyzing changes of cell properties from in vivo to in vitro and by the cell separation to enrich specific cell types in preparation. Furthermore, evidence has been accumulated suggesting that the properties of epithelial cells in culture are part of the integral cellular physiologies of epithelial cells in vivo. These properties are, in most cases, related to cell injury which is reparable even in vitro if the appropriate condition is provided. Using the airway epithelial cell culture system developed in our laboratory as an example, the above points are discussed. Finally, we have shown that a differentiated tracheal epithelium with a similar polarity as in vivo was established in the described serum-free culture condition.

Animals↗
PubMed1992

Epithelial differentiation in gliomas, meningiomas and choroid plexus papillomas.

The immunohistological findings using antibodies to different intermediate filaments (glial fibrillary acidic protein, vimentin and two types of cytokeratin) and epithelial membrane antigen are described in 89 gliomas, 19 meningiomas and 8 choroid plexus papillomas (CPPs) from adult patients. All the patients had total or subtotal surgical excision of their tumours with clinical follow up for between 3 and 7 years. The immunohistological results were correlated with the histological features and patient survival. Tumours other than low grade astrocytomas, oligodendrogliomas and anaplastic ependymomas expressed one or more epithelial markers. This immunohistological evidence of epithelial differentiation in the absence of histological epithelial features in gliomas confirms that the two are not necessarily correlated. It is concluded that the expression of epithelial markers in some intradural tumours may reflect aberrant differentiation related to the degree of anaplasia in poorly differentiated astrocytomas and glioblastomas. All the patients with anaplastic epithelial marker-positive gliomas died within 1 year, whereas only 68% of patients with marker-negative tumours died within the follow-up period. In ependymomas and meningiomas, the expression of epithelial markers may reflect their histogenesis, while in malignant CPPs such expression could denote either their aberrant differentiation or histogenetic derivation.

Adolescent↗
PubMed2002

Epithelial differentiation promotes the adherence of type 1-piliated Escherichia coli to human vaginal cells.

Colonization of the vaginal introitus by fecal Escherichia coli is thought to be a key initial event leading to acute urinary tract infection, yet the mannosylated receptor for type 1 pili on the squamous epithelium of vaginal mucosa is unknown. E. coli expressing type 1 pili adhered to sections of normal human vaginal epithelium in a gradient with greatest binding in upper cell layers was observed, which suggests that epithelial differentiation influences bacterial binding. Consistent with this observation, bacterial binding was enhanced in vaginal epithelial cultures that were induced to differentiate, and this enhanced bacterial binding was associated with increased K13 expression levels and increased binding of the mannose-specific lectin Galanthus nivalis agglutinin. These results demonstrate that the binding of type 1-piliated E. coli to vaginal epithelial cells correlates with epithelial differentiation and suggest that the vaginal receptor for type 1 pili is up-regulated during differentiation.

Bacterial Adhesion↗
PubMedDate not supplied

Cytokeratin expression patterns in the rat respiratory tract as markers of epithelial differentiation in inhalation toxicology. I. Determination of normal cytokeratin expression patterns in nose, larynx, trachea, and lung.

Cytokeratin (CK) polypeptides constitute the intermediate filament cytoskeleton of epithelial cells. The patterns of CK expression can be regarded as specific markers for the epithelial differentiation status. Our objective was to map the cell type-specific CK expression patterns at all representative sites of the respiratory tract of untreated rats to use as a base for the detection of inhalation exposure-related differentiation changes. Using routine paraffin-embedded sections and a panel of well-characterized monoclonal antibodies for immunohistochemistry, we obtained CK staining patterns as follows. Nasal cavity: respiratory epithelium CK18, CK19 (basal, ciliated, nonciliated cells), CK14, and/or CK15 (basal and nonciliated cells); olfactory epithelium CK18 (basal, mid, apical zones and Bowman's glands), CK14, and CK15 (basal zone); squamous epithelium of ventral meatus CK14, CK15 (basal and suprabasal cells), CK1, 10/11, and CK13 (suprabasal cells); glands and columnar epithelia of vomeronasal organ and nasolacrimal duct CK7 and CK13 in addition to respiratory epithelial CK pattern. Trachea: similar to nasal respiratory epithelium with pronounced CK15 and additional CK7. Larynx: CK14, CK15 (basal, ciliated, nonciliated cells), CK8, CK18, CK19 (not in basal cells), CK4, and CK13 (cuboidal and squamoid cells of ventral half). Lung: bronchial epithelium CK14 and CK15 (basal cells only); bronchial and alveolar epithelium CK7, CK8, CK18, and CK19; bronchiolar epithelium similar but less CK8 and no CK7; pleural mesothelium CK7, CK8, and CK19. This inventory of complex CK expression patterns provides the basis for investigating test substance-related effects in inhalation toxicology, e.g., cigarette smoke-induced changes.

Animals↗
PubMed1993

Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cells transformed with a temperature-sensitive v-SRC gene.

Loss of histotypic organization of epithelial cells is a common feature in normal development as well as in the invasion of carcinomas. Here we show that the v-src oncogene is a potent effector of epithelial differentiation and invasiveness. MDCK epithelial cells transformed with a temperature-sensitive mutant of v-src exhibit a strictly epithelial phenotype at the nonpermissive temperature for pp60v-src activity (40.5 degrees C) but rapidly loose cell-to-cell contacts and acquire a fibroblast-like morphology after culture at the permissive temperature (35 degrees C). Furthermore, the invasiveness of the cells into collagen gels or into chick heart fragments was increased at the permissive temperature. The profound effects of v-src on intercellular adhesion were not linked to changes in the levels of expression of the epithelial cell adhesion molecule E-cadherin. Rather, we observed an increase in tyrosine phosphorylation of E-cadherin and, in particular, of the associated protein beta-catenin. These results suggest a mechanism by which v-src counteracts junctional assembly and thereby promotes invasiveness and dedifferentiation of epithelial cells through phosphorylation of the E-cadherin/catenin complex.

Animals↗
PubMed1999

Two novel promoters in the upstream regulatory region of human papillomavirus type 31b are negatively regulated by epithelial differentiation.

Organotypic cultures support the stratification and differentiation of keratinocytes and the human papillomavirus (HPV) life cycle. We report transcription from four novel promoters in the HPV31b upstream regulatory region during the viral life cycle in organotypic cultures. Promoter initiation was not differentiation dependent; two promoters were down-regulated upon epithelial differentiation.

Base Sequence↗
PubMed2006

Expression of gamma-aminobutyric acid and glutamic acid decarboxylases in rat descending colon and their relation to epithelial differentiation.

OBJECTIVE: To detect the expression of gamma-aminobutyric acid (GABA) and glutamic acid decarboxylases (GADs; including two isoforms GAD65 and GAD67) in the epithelial growth zones of the descending colon in rats, and to investigate their relation to epithelial differentiation and proliferation. METHODS: The expression of GABA and GADs in rat descending colon was investigated by immunofluorescent staining and confocal laser scanning techniques, and goblet cells were further investigated by wheat-germ agglutinin histochemistry. In addition, GAD65 and GAD67 mRNAs were also detected by reverse transcription-polymerase chain reaction. Furthermore, evaluation of cell kinetics in colonic epithelia was conducted by ABC immunostaining using a monoclonal antibody against proliferating cell nuclear antigen (PCNA). RESULTS: Immunoreactive GABA and GADs were distributed in the upper third of the crypts and at the luminal surface in the rat descending colon. Strong staining for GABA and GADs was localized mainly in the cytoplasm of epithelial cells near the neck of the crypts and along the luminal surface. In addition, GABA and GAD65 were also detected at the lamina propria in colonic mucosa. No staining for GABA or GADs was found in goblet cells. GAD65 and GAD67 mRNAs were identified in homogenates of rat descending colon. PCNA labeled nuclei were found in the lower two-thirds of the crypts. CONCLUSIONS: The expression of GABA and GADs in the maturation and function zones of rat descending colon suggests that GABA may be involved in the differentiation of colonic epithelial cells.

Animals↗
PubMed1995

Epithelial differentiation in the mouse preimplantation embryo: making adhesive cell contacts for the first time.

The preimplantation embryo generates two distinct tissues, the trophectoderm, which is a transporting polarized epithelium, and the inner cell mass. Epithelial differentiation and tissue segregation, here examined in relation to the maturation of membrane adhesion and cell junction systems, are coordinated events regulated by a combination of the zygotic gene expression programme, kinase-mediated protein activation and cell-cell interactions.

Animals↗
PubMed1992

Intermediate filaments and epithelial differentiation of male rat embryonic gonad.

The presence and distribution of desmin, vimentin, cytokeratin, and laminin in the gonads of developing male rat embryos (11-17 days) were studied by immunocytochemistry. The findings were correlated with morphological changes of the cells and with the formation of basement membranes, as determined by electron microscopy. The surface epithelial and subepithelial cells of the meesonephros in the prospective gonadal region contained desmin. At the onset of gonadal development, vimentin appeared in the somatic cells of the thickening surface epithelium, which formed the gonadal ridge. Desmin disappeared and cytokeratins appeared in the Sertoli precursor cells at the inception of their epithelial differentiation. Simultaneously, the prospective Sertoli cells became polarized during their assembly into epithelial cell aggregates; the aggregates then fused and formed elongated testicular cords. The epithelial cell differentiation was accompanied by a deposition of basement membrane material around the cords and by an increase of desmin in the cells immediately around the cords. With further differentiation of the testicular cords, some cytokeratins from the Sertoli cells, but not from the cells of the rete cords, disappeared. On the other hand, other cytokeratin polypeptides and vimentin remained in the fetal Sertoli cells. The surface cell layer slowly differentiated towards a proper epithelium after the basic formation of the testicular cords and interstitium. Desmin and vimentin persisted in the interstitial cells throughout the entire study period. The early differentiation of the gonad is apparently under a general sex-independent initiation program. The developmental changes in intermediate filaments offer an opportunity for the further analysis of their general role in early organogenesis. In light of the genetic theory of testicular differentiation, the functions of the regulatory factor(s) include specific organization of cord cells, histological organization into looping cords rather than separated follicles, and male development of the interstitium, surface epithelium and tunica albuginea.

Animals↗