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991.
Gast D Riedle S Kiefel H Müerköster SS Schäfer H Schäfer MK Altevogt P 《Experimental cell research》2008,314(13):2411-2418
L1 cell adhesion molecule (L1-CAM) is a transmembrane cell adhesion molecule initially defined as a promigratory molecule in the developing nervous system. L1 is also overexpressed in a variety of human carcinomas and is associated with bad prognosis. In carcinoma cell lines L1 augments cell motility and metastasis, tumor growth in nude mice and induces expression of L1-dependent genes. It is not known whether L1-signaling requires ligand binding. The RGD motif in the sixth Ig domain of L1 is a binding site for integrins. In the present study we analyzed the role of RGDs in L1-signaling using site-directed mutagenesis combined with antibody blocking studies. We observed that L1-RGE expressing HEK293 cells showed reduced cell–cell binding, cell motility, invasiveness and tumor growth in NOD/SCID mice. The RGE-mutation impaired L1-dependent gene regulation and antibodies to αvβ5 integrin had similar effects. Mutant L1 was unable to translocate to the nucleus. Our findings highlight the importance of the RGD site in L1 for human tumors and suggest that nuclear signaling of L1 is dependent on integrins. 相似文献
992.
993.
Identification and characterization of an essential telomeric repeat binding factor in fission yeast 总被引:1,自引:0,他引:1
Whereas mammalian cells harbor two double strand telomeric repeat binding factors, TRF1 and TRF2, the fission yeast Schizosaccharomyces pombe has been thought to harbor solely the TRF1/TRF2 ortholog Taz1p to perform comparable functions. Here we report the identification of telomeric repeat binding factor 1 (Tbf1), a second TRF1/TRF2 ortholog in S. pombe. Like the Taz1p, the identified Tbf1p shares amino acid sequence similarity, as well as structural and functional characteristics, with the mammalian TRF1 and TRF2 proteins. This family of proteins shares a common architecture with two separate structural domains. An N-terminal domain is necessary and sufficient for the formation of homodimers, and a C-terminal MYB/homeodomain mediates sequence specific recognition of double-stranded telomeric DNA. The identified Tbf1p binds S. pombe telomeric DNA with high sequence specificity in vitro. Targeted deletion of the tbf1 gene reveals that it is essential for survival, and overexpression of the tbf1 gene leads to telomere elongation in vivo, which is dependent upon the MYB domain. These data suggest that fission yeast, like mammals, have two factors that bind double-stranded telomeric DNA and perform distinct roles in telomere length regulation. 相似文献
994.
995.
Nervous system tumors are one of the leading causes of cancer related death. Specific mechanisms facilitating the invasive
behavior of gliomas remain obscure. Advanced simulation models of the in vivo response to therapy conditions should potentially
improve malignant glioma treatment. Expressional profiling of vimentin––one of reliable pro-invasive tumor makers––in those
simulation models was the goal of this study, in order to estimate a pro-invasive response of surviving malignant glioma cells
under clinically relevant therapeutic conditions. Human U87-MG malignant glioma cells were used. These cells are characterized
by the wild p53-phenotype, which is relevant for the majority of primary malignant glioblastomas. Experimental design foresaw the cells to
undergo either irradiation or chemo-treatment with temozolomide alone, or combined treatment. Expression profiling of vimentin
was performed by quantitative “Real-Time”-PCR under all treatment conditions simulating diverse tumor regions. Here we demonstrated
that vimentin expression patterns in human malignant glioma cells strongly depend on cellular density, algorithms of drug
delivery and chemo/radio treatment. Substantial differences were recognized between immediate and late therapy effects. Significant
increase in vimentin expression levels was detected particularly in low-density cell cultures under durable treatment with
constant concentration levels of temezolomide. Simulation of variable intratumoral regional conditions (central intratumoral
regions vs. disseminated malignant cells in peripheral regions) demonstrated differential response of vimentin expression
in malignant glioma cell cultures treated under clinically relevant conditions. Slight ebbing of expression levels as late
effects of the treatment in confluent cultures may correspond to necrotic processes clinically observed in central intratumoral
regions. Contrary, in disseminated malignant cells of peripheral regions therapy resulted in vimentin-inducing effects. This
is in agreement with the clinical observations of an increased aggressiveness and malignancy grade of post-operatively chemo/radio-treated
malignant gliomas. 相似文献
996.
997.
Best D Sahlender DA Walther N Peden AA Adams IR 《Development (Cambridge, England)》2008,135(8):1415-1425
In mammals, the supporting cell lineage in an embryonic gonad communicates the sex-determining decision to various sexually dimorphic cell types in the developing embryo, including the germ cells. However, the molecular nature of the sex-determining signals that pass from the supporting cells to the germ cells is not well understood. We have identified a conserved transmembrane protein, Sdmg1, owing to its male-specific expression in mouse embryonic gonads. Sdmg1 is expressed in the Sertoli cells of embryonic testes from 12.5 dpc, and in granulosa cells of growing follicles in adult ovaries. In Sertoli cells, Sdmg1 is localised to endosomes, and knock-down of Sdmg1 in Sertoli cell lines causes mis-localisation of the secretory SNARE Stx2 and defects in membrane trafficking. Upregulation of Sdmg1 appears to be part of a larger programme of changes to membrane trafficking pathways in embryonic Sertoli cells, and perturbing secretion in male embryonic gonads in organ culture causes male-to-female germ cell sex reversal. These data suggest that changes that occur in the cell biology of embryonic Sertoli cells may facilitate the communication of male sex-determining decisions to the germ cells during embryonic development. 相似文献
998.
999.
The Salmonella enterica serotype Typhimurium ( S. typhimurium ) genome contains a large repertoire of putative fimbrial operons that remain poorly characterized because they are not expressed in vitro . In this study, insertions that induced expression of the putative stdABCD fimbrial operon were identified from a random bank of transposon mutants by screening with immuno-magnetic particles for ligand expression (SIMPLE). Transposon insertions upstream of csgC and lrhA or within dam , setB and STM4463 (renamed rosE ) resulted in expression of StdA and its assembly into fimbrial filaments on the cell surface. RosE is a novel negative regulator of Std fimbrial expression as indicated by its repression of a std :: lacZ reporter construct and by binding of the purified protein to a DNA region upstream of the stdA start codon. Expression of Std fimbriae in the rosE mutant resulted in increased attachment of S. typhimurium to human colonic epithelial cell lines (T-84 and CaCo-2). A rosE mutant exhibited a reduced ability to compete with virulent S. typhimurium for colonization of murine organs, while no defect was observed when both competing strains carried a stdAB deletion. These data suggest that a tight control of Std fimbrial expression mediated by RosE is required during host pathogen interaction. 相似文献
1000.
Klusackova P Lebedova J Kacer P Kuzma M Brabec M Pelclova D Fenclova Z Navratil T 《Prostaglandins, leukotrienes, and essential fatty acids》2008,78(4-5):281-292
Exhaled breath condensate (EBC) contains many substances, which could help in diagnosis of occupational asthma. The aim of the study is to monitor leukotrienes (LT) and 8-isoprostane from EBC in bronchoprovocation tests with allergens in 47 patients with suspected occupational asthma. Forty-one patients were tested negative. In negative bronchoprovocation tests, no significant differences (P<0.05) were seen between the five measurements during and after the test. In control measurements (without provocation), significant differences were found among four measurements done within 24h for 8-isoprostane (P=0.0138). The relationship between the log transformed ratios of the EBC parameters and FEV(1) was never significant at the 5% level in control measurements, while in negative tests, statistical significance was recorded for LTB(4) (P=0.0299) before and 5h after the test. Six of 47 patients were tested positive. Such a small number of patients did not allow proper statistical analysis and therefore, the results are described separately for each patient. 相似文献