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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Archives of dermatological research 277 (1985), S. 377-383 
    ISSN: 1432-069X
    Keywords: Type-IV procollagen ; Laminin ; EGF ; TPA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) and epidermal growth factor (EGF) on type-IV-procollagen (basement-membrane collagen) and laminin synthesis, turnover, and secretion was studied in human A431 squamous epidermoid carcinoma cells. Type-IV procollagen and laminin were biochemically and immunologically identified in the medium and cell extracts using immunoprecipitation followed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. EGF or TPA produced a sixfold increase in type-IV-procollagen and laminin secretion within 2 h; this was accompanied by a three-to fourfold increase in the levels of cell-associated type-IV procollagen and laminin, respectively. The level of type-IV-procollagen and laminin synthesis and secretion remained elevated for at least 16 h after the administration of either EGF or TPA. A combination of EGF and TPA was more effective than either agent alone in promoting the secretion of laminin but not of type-IV procollagen. EGF and/or TPA did not, however, produce a selective increase in the synthesis of collagen and laminin, since total protein synthesis was also increased to the same degree by these agents. As dtermined by labeling and chase studies, neither EGF nor TPA had any appreciable effect upon type-IV-procollagen or laminin degradation. These results indicate that the synthesis of components associated with the basement membrane in A431 cells (i.e., type-IV procollagen and laminin) can be rapidly modulated by EGF and a tumor promoter, i. e., TPA. The increase in extracellular-matrix-protein production precedes any effects of these agents on cell growth. However, changes in cell shape in response to either EGF or TPA may trigger the increase in the synthesis and secretion of type-IV procollagen and laminin.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Breast cancer research and treatment 29 (1994), S. 11-27 
    ISSN: 1573-7217
    Keywords: amphiregulin ; autocrine growth regulation ; c-erbB-2 ligands ; cripto ; epidermal growth factor ; EGF receptor ligands ; heregulin ; HER-2/neu ligands ; juxtacrine growth factors ; transforming growth factor α
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A number of different epidermal growth factor (EGF)-related peptides such as EGF, transforming growth factor α (TGFα), amphiregulin (AR), heregulin (HRG), and cripto-1 (CR-1), are coexpressed to varying degrees in both normal and malignant mammary epithelial cells. However, in general the frequency and level of expression of TGFα, AR, and CR-1 are higher in malignant breast epithelial cells than in normal mammary epithelium. In addition, several of these peptides such as TGFα and AR can function as autocrine and/or juxtacrine growth factors in mammary epithelial cells, and their expression is stringently regulated by mammotrophic hormones such as estrogens, activated proto-oncogenes that have been implicated in the pathogenesis of breast cancer, and other growth factors. The redundancy of expression that is observed for a number of these structurally related peptides in both normal and malignant mammary epithelial cells suggests that some of these peptides may be involved in regulating other aspects of cellular behavior such as differentiation in addition to proliferation.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Molecular Reproduction and Development 41 (1995), S. 277-286 
    ISSN: 1040-452X
    Keywords: EGF-like ligands ; Postnatal development ; RT-PCR ; Immunocytochemistry ; Immunoblotting ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Amphiregulin (Ar) and Cripto-1 (Cr-1) are growth promoting peptides that share amino acid sequence homology with epidermal growth factor (EGF). The present study examined Ar and Cr-1 mRNA and protein expression during various stages of C57BL/6 mouse mammary morphogenesis. Reverse transciption-polymerase chain reaction (RT-PCR) was used to detect transcripts for Ar and Cr-1 at all stages of mammary development. Immunocytochemical (ICC) localization demonstrated that in virgin 4-week to mature 12-week-old mouse fourth inguinal mammary gland, Ar and Cr-1 are expressed in the stromal cells, luminal epithelial cells, and myoepithelial cells of the branching ducts. Ar, and to lesser extent Cr-1, were also found in the epithelial cap cells and in the luminal epithelial cells of the advancing terminal end bud (TEB) from virgin 4-week and 6-week-old mice. Western blot analysis demonstrated that both Ar (28 and 26 kDa) and Cr-1 (90, 67, 56, and 21 kDa) proteins are expressed in virgin, 13.5 day midpregnant and in the 14 day lactating mammary gland. In addition, Ar and Cr-1 are associated with developing alveolar structures as determined by ICC. These results imply that together with EGF and transforming growth factor alpha (TGFα), Ar and Cr-1 may play salient roles as modifiers in the morphogenesis and differentiation of the mammary gland. © 1995 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 11 (2000), S. 319-325 
    ISSN: 1569-8041
    Keywords: antisense oligonucleotides ; EGF-related peptides ; ovarian carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background:The epidermal growth factor (EGF)-like peptides CRIPTO(CR), amphiregulin (AR) and transforming growth factor α (TGFα) areexpressed in human ovarian carcinomas. Materials and methods:The expression of AR, CR and TGFα inovarian carcinoma cell lines was assessed by immunocytochemistry and reversetranscriptase–polymerase chain reaction (RT–PCR). Theantiproliferative effects of antisense phosphorothioate oligodeoxynucleotides(AS S-Oligos) directed against either AR, CR or TGFα was evaluated byusing a clonogenic assay. Results:A majority of the ovarian carcinoma cell lines was foundto express TGFα, AR and CR mRNAs and proteins. AS S-Oligos directedagainst either AR, CR or TGFα were able to inhibit theanchorage-independent growth of NIH:OVCAR3 and NIH:OVCAR8 cells in a dosedependent manner. A 30%–50% growth inhibition was observedat a 2 µM concentration of the AS S-Oligos. Treatment of these cellswith combinations of EGF-related AS S-Oligos resulted in a more significantgrowth inhibition when compared to treatment with a single AS S-oligo. A60%–75% growth inhibition was observed using combinationsof AR, CR and TGFα AS S-oligos at a total concentration of 2 µM. Anadditive growth-inhibitory effect occurred when ovarian carcinoma cells wereexposed to the AS S-Oligos after treatment with either paclitaxel orcis-platinum. Conclusions:These data suggest that EGF-related peptides functionas autocrine growth factors in ovarian carcinoma cells, and that they mightrepresent targets for experimental therapy of ovarian carcinoma.
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 156 (1993), S. 497-514 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: To ascertain if 17β-estradiol (E2)-induced proliferation could be attenuated by blocking the expression of endogenous transforming growth factor α (TGFα), estrogen receptor (ER)-positive, estrogen-responsive MCF-7 or ZR-75-1 cells and ER-negative, estrogen-nonresponsive MDA-MB-468 or HS-578T cells were infected with a recombinant amphotropic, replication-defective retroviral expression vector containing a 435 base pair (bp) Apa1-Eco R1 coding fragment of the human TGFα cDNA oriented in the 3′ to 5′ direction and under the transcriptional control of an internal heavy metal-inducible mouse metallothionein (MT-1) promoter and containing the neomycin (neo) resistance gene. E2-stimulated expression of endogenous TGFα mRNA was inhibited by 4-5-fold, and the production of TGFα protein was inhibited by 50-80% when M-1 mass-infected MCF-7 or MZ-1 mass-infected ZR-75-1 cells were treated with 0.75-1 μM CdCl2, whereas in comparably treated parental MCF-7 or ZR-75-1 cells there was no significant effect upon these parameters. E2-stimulated anchorage-dependent growth (ADG) and anchorage-independent growth (AIG) of the M-1 or MZ-1 cells was inhibited by 60-90% following CdCl2 treatment. In contrast, neither the ADG nor AIG of the parental noninfected MCF-7 or ZR-75-1 cells that were maintained in the absence or presence of E2 was affected by comparable concentrations of CdCl2. The ADG and AIG of TGFα antisense MD-1 mass-infected MDA-MB-468 cells that express high levels of endogenous TGFα mRNA were also inhibited by 1 μM CdCl2, whereas the ADG and AIG of MH-1 mass-infected HS-578T cells, a TGFα-negative cell line, were unaffected by CdCl2 treatment. These results suggest that TGFα may be one important autocrine intermediary in regulating estrogen-induced cell proliferation. © 1993 Wiley-Liss, Inc.
    Additional Material: 11 Ill.
    Type of Medium: Electronic Resource
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