共查询到20条相似文献,搜索用时 15 毫秒
1.
Kitayoshi M Fukui R Tanabe E Kato K Yoshikawa K Fukushima N Tsujiuchi T 《Journal of receptor and signal transduction research》2012,32(4):209-213
Lysophosphatidic acid (LPA) receptors belong to G protein-coupled transmembrane receptors and mediate a variety of cellular responses through the binding of LPA. So far, six types of LPA receptors (LPA receptor-1 (LPA?) to LPA?) have been identified. Recently, it has been demonstrated that each LPA receptor has opposite effects on malignant property of cancer cells. In this study, to evaluate an involvement of LPA receptors on angiogenic process in mammary tumor cells, we generated Lpar1- and Lpar3-expressing (FM3A-a1 and FM3A-a3A9, respectively) cells from FM3A cells, and investigated the effects on cell proliferation and migration abilities of endothelial F-2 cells by those cells. In Vegf-A and Vegf-C genes, FM3A-a1 cells indicated high expression and FM3A-a3A9 cells showed low expression, compared with control cells. When F-2 cells were cultured with a supernatant from FM3A-a1 cells, the cell growth rate and migration ability of F-2 cells was significantly higher than control cells. By contrast, a supernatant from FM3A-a3A9 cells significantly inhibited those abilities of F-2 cells. These results suggest that LPA? and LPA? may play opposite roles on the regulation of endothelial cells in mouse mammary tumor FM3A cells. 相似文献
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Epigenetic activation of α4, β2 and β6 integrins involved in cell migration in trichostatin A-treated Hep3B cells 总被引:4,自引:0,他引:4
Summary The epigenetic modulation by histone deacetylase (HDAC) inhibitors including trichostatin A (TSA) has been known to block
cell proliferation, induce apoptosis and inhibit cell migration in human cancer cells that represents the potential therapeutic
agents for cancers and fibrosis. However, more than 55% of Hep3B cells remained alive after our initial study of 100 nM TSA
treatment. To further study the epigenetic modulation and the biological function of newly activated genes by HDAC inhibitor
involved in HCC progression and metastasis, we profiled 23 integrin genes including 15α and 8β in TSA-treated Hep3B cells.
Six integrins including three down-regulated α6, α10, β8 and three significant up-regulated α4, β2, β6 integrins were revealed
after semi-quantitative RT-PCR. To confirm the epigenetic modulation and explore their biological functions, we selected the
three significantly up-regulated integrins for confirmation of protein up-regulation, hyperacetylated-histones by ChIP assays,
and functional inhibition by specific neutralizing antibodies of integrins. Our results indicated that epigenetic modulation
in TSA-treated Hep3B cells up-regulated new integrins including α4, β2 and β6 and reduced migration activities by specific
neutralizing antibodies to 61.3%, 42.4% and 34.5%, respectively. Our novel findings provided a better understanding of the
epigenetic modulation of integrins and suggested that targeting the epigenetic up-regulated integrins to abrogate the migration
activity might be a promising strategy to prevent HCC progression. 相似文献
4.
During wound healing and cancer metastasis, cells are frequently observed to migrate in collective groups. This mode of migration relies on the cooperative guidance of leader and follower cells throughout the collective group. The upstream determinants and molecular mechanisms behind such cellular guidance remain poorly understood. We use live-cell imaging to track the behavior of epithelial sheets of keratinocytes in response to transforming growth factor β (TGFβ), which stimulates collective migration primarily through extracellular regulated kinase 1/2 (Erk1/2) activation. TGFβ-treated sheets display a spatial pattern of Erk1/2 activation in which the highest levels of Erk1/2 activity are concentrated toward the leading edge of a sheet. We show that Erk1/2 activity is modulated by cellular density and that this functional relationship drives the formation of patterns of Erk1/2 activity throughout sheets. In addition, we determine that a spatially constrained pattern of Erk1/2 activity results in collective migration that is primarily wound directed. Conversely, global elevation of Erk1/2 throughout sheets leads to stochastically directed collective migration throughout sheets. Our study highlights how the spatial patterning of leader cells (cells with elevated Erk1/2 activity) can influence the guidance of a collective group of cells during wound healing. 相似文献
5.
M. Durante G. F. Grossi G. Gialanella M. Pugliese M. Nappo T. C. Yang 《Radiation and environmental biophysics》1995,34(3):195-204
We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of -particles emitted from radon daughters, we concentrated our studies on the efficiency of -particles. Confluent cultures of M/10 cells were exposed to accelerated -particles [beam energy incident at the cell monolayer=3.85 MeV, incident linear energy transfer (LET) in cell= 109 keV/µm] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for -particles (D0 = 0.73± 0.04 Gy), while a shoulder was observed for x-rays (/ = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET -particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for cc-particles and linear-quadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges. The RBE for the induction of total chromosome aberrations (2.3 at 37% cell survival) was lower than that for cell survival, suggesting that chromosome damage at the first postirradiation mitosis is not sufficient to account for the increased efficiency of -particles in the induction of lethal effects. However, measured cell survival after -particle irradiation can be predicted from chromosome damage when cells at different population doubling numbers after irradiation are considered. In fact, a high percentage of -irradiated cells carried unstable chromosomal aberrations up to population doubling number about 5. On the other hand, x-ray-induced damage disappeared rapidly. These results suggest that -particle-induced reproductive death of human mammary epithelial cells is caused by chromosome damage in the first 5 generations following exposure, whereas the in-activation produced by low-LET radiation is mostly related to the aberrations at the first post-irradiation mitosis. 相似文献
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Kimie Date Tomomi Yamazaki Yoko Toyoda Kumi Hoshi Haruko Ogawa 《Journal of cellular biochemistry》2020,121(2):1238-1249
α-Amylase, which plays an essential role in starch degradation, is expressed mainly in the pancreas and salivary glands. Human α-amylase is also detected in other tissues, but it is unclear whether the α-amylase is endogenously expressed in each tissue or mixed exogenously with one expressed by the pancreas or salivary glands. Furthermore, the biological significance of these α-amylases detected in tissues other than the pancreas and salivary glands has not been elucidated. We discovered that human α-amylase is expressed in intestinal epithelial cells and analyzed the effects of suppressing α-amylase expression. α-Amylase was found to be expressed at the second-highest messenger RNA level in the duodenum in human normal tissues after the pancreas. α-Amylase was detected in the cell extract of Caco-2 intestinal epithelial cells but not secreted into the culture medium. The amount of α-amylase expressed increased depending on the length of the culture of Caco-2 cells, suggesting that α-amylase is expressed in small intestine epithelial cells rather than the colon because the cells differentiate spontaneously upon reaching confluence in culture to exhibit the characteristics of small intestinal epithelial cells rather than colon cells. The α-amylase expressed in Caco-2 cells had enzymatic activity and was identified as AMY2B, one of the two isoforms of pancreatic α-amylase. The suppression of α-amylase expression by small interfering RNA inhibited cell differentiation and proliferation. These results demonstrate for the first time that α-amylase is expressed in human intestinal epithelial cells and affects cell proliferation and differentiation. This α-amylase may induce the proliferation and differentiation of small intestine epithelial cells, supporting a rapid turnover of cells to maintain a healthy intestinal lumen. 相似文献
7.
Changgong Li Aimin Li Yiming Xing Lingyan Hu Stewart Anderson Parviz Minoo 《Developmental biology》2009,334(1):97-124
The precise mechanisms by which β-catenin controls morphogenesis and cell differentiation remain largely unknown. Using embryonic lung development as a model, we deleted exon 3 of β-catenin via Nkx2.1-cre in the Catnb[+/lox(ex3)] mice and studied its impact on epithelial morphogenesis. Robust selective accumulation of truncated, stabilized β-catenin was found in Nkx2.1-cre;Catnb[+/lox(ex3)] lungs that were associated with the formation of polyp-like structures in the trachea and main-stem bronchi. Characterization of polyps suggests that accumulated β-catenin impacts epithelial morphogenesis in at least two ways. “Intracellular” accumulation of β-catenin blocked differentiation of spatially-appropriate airway epithelial cell types, Clara cells, ciliated cells and basal cells, and activated UCHL1, a marker for pulmonary neuroendocrine cells. There was also evidence for a “paracrine” impact of β-catenin accumulation, potentially mediated via activation of Bmp4 that inhibited Clara and ciliated, but not basal cell differentiation. Thus, excess β-catenin can alter cell fate determination by both direct and paracrine mechanisms. 相似文献
8.
Talhouk RS Khalil AA Bajjani R Rahme GJ El-Sabban ME 《Cell communication & adhesion》2011,18(5):104-116
Crosstalk between gap junction intracellular communication (GJIC), STAT5 and OCT-1 in gap junction (GJ)-dependent β-casein expression was investigated. CID-9 mammary cells plated with prolactin on non-adherent substratum (poly-HEMA) expressed β-casein independent of STAT5 only in the presence of the GJIC inducer, cAMP. Nuclear STAT5 levels were not detectable. By contrast, cells on EHS-drip expressed β-casein in a STAT5-dependent manner and nuclear STAT5 levels were up-regulated. A 75 kDa OCT-1 isoform was detected in conditions that induced β-casein expression regardless of substratum. Interestingly, 40 and 28 kDa OCT-1 isoforms were induced in cells on polyHEMA with cAMP. Electrophoretic mobility shift assays (EMSA) for OCT-1 revealed two band shifts in cells on polyHEMA with cAMP and on EHS-drip, which were repressed by the GJIC inhibitor, 18α-GA. These studies demonstrated that mammary cells on polyHEMA expressed β-casein in response to prolactin in a pathway that involves GJIC and OCT-1 and is independent of STAT5 nuclear translocation. 相似文献
9.
Akira Ikari Kosuke Atomi Keishi Kinjo Yohei Sasaki Junko Sugatani 《Life sciences》2010,86(19-20):766-773
AimsLoss of magnesium (Mg2+) inhibits cell proliferation and augments nephrotoxicant-induced renal injury, but the role of Mg2+ has not been clarified in detail. We examined the effect of extracellular Mg2+ deprivation on a MEK–ERK cascade and cell proliferation using a renal epithelial cell line, Madin-Darby canine kidney (MDCK) cells.Main methodsMDCK cells were cultured in Mg2+-containing or Mg2+-free media. A HA-tagged constitutively active (CA)-MEK1 and a dominant negative (DN)-MEK1 were transfected into MDCK cells. The level of protein was examined by Western blotting. The intracellular free Mg2+ concentration ([Mg2+]i) was measured using a fluorescent dye, mag-fura 2. Cell proliferation was determined by WST-1 assay. Dead cells were identified by staining with annexin V-FITC and propidium iodide.Key findingsIn the presence of fetal calf serum (FCS), Mg2+ deprivation decreased phosphorylated-ERK1/2 (p-ERK1/2) levels and [Mg2+]i. Re-addition of Mg2+ increased p-ERK1/2 levels, which were inhibited by U0126, a specific inhibitor of a MEK–ERK cascade. Glutathione-S-transferase pull-down and coimmunoprecipitation assays showed that CA-MEK1 and DN-MEK1 binds with ERK1/2 in the presence of Mg2+. In contrast, neither CA-MEK1 nor DN-MEK1 bound to ERK1/2 in the absence of Mg2+. These results indicate that the MEK–ERK cascade is regulated by [Mg2+]i. Cell proliferation was increased by the treatment with FCS or the expression of CA-MEK1 in the presence of Mg2+, but was inhibited by Mg2+ deprivation. Mg2+ deprivation did not increase the number of dead cells.SignificanceMg2+ is involved in the regulation of the MEK–ERK cascade and cell proliferation in MDCK cells. 相似文献
10.
Petrovic L Pohle D Münstedt H Rechtenwald T Schlegel KA Rupprecht S 《Journal of biomedical science》2006,13(1):41-46
Summary Non-resorbable thermoplastic polymers have become more important for reconstructive surgery due to their excellent chemical
and physical properties. Polyetheretherketone-β-tricalcium phosphate (βTCP-PEEK) composites were developed as alternative
materials for load-bearing applications. This study presents the effect of polyetheretherketone (PEEK) specimens incorporated
with 5, 10, 20 and 40 wt% β-tricalcium phosphate (βTCP) and processed by injection molding on cultivated osteoblast cells.
Normal human osteoblast (NHOst) cells were seeded onto polymer discs to evaluate cell viability and proliferation after 24,
72 and 120 h of cultivation by employing the WST-1 assay. Standard tissue culture plastic was used as a control. The osteoblast
cells were found to be viable in all PEEK groups, while the cell proliferation was progressively inhibited due to the incorporated
β-tricalcium phosphate. βTCP-PEEK showed concentration independent decrease of cell proliferation compared to the unfilled
PEEK and the control group. In summary, this study confirms the non-toxic nature of pure PEEK, whereas this could not definitely
be verified for βTCP-PEEK as a composite material in chosen concentrations of β-tricalcium phosphate in vitro. 相似文献
11.
Midori Hosobuchi Martha R. Stampfer 《In vitro cellular & developmental biology. Plant》1989,25(8):705-713
Summary Normal human mammary epithelial cells (HMEC) from different individual reduction mammoplasty specimens were all growth inhibited,
and showed a flattened, elongated morphology in response to human recombinant transforming growth factor β1 (TGFβ). The degree
of growth inhibition varied among specimens, but none of the normal HMEC maintained growth in the continued presence of TGFβ.
The degree of growth inhibition also varied with cell age in vitro, cells closer to senescence being more sensitive. TGFβ
sensitivity was additionally assayed in two established cell lines derived from one of the reduction mammoplasty specimens
after exposure to benzo(a)pyrene. Although varying degrees of growth inhibition and morphologic changes were observed in the
cell lines, both lines contained populations that maintained active growth in the presence of TGFβ. Subclones of these lines
demonstrated a great plasticity in their growth response to TGFβ, with individual clones ranging from strongly growth inhibited
to nearly unaffected. These results suggest that multiple factors influence the extent of TGFβ-induced growth effects on both
normal and transformed mammary epithelial cells, and that some of these factors may act through epigenetic mechanisms.
This work was supported by CA24844 from the National Institutes of Health, Bethesda, MD, and the Office of Energy Research,
Office of Health and Environmental Research of the U.S. Department of Energy under contract DE-AC03-76SF00098. 相似文献
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Mutation of tyrosine residue 857 in the PDGF β-receptor affects cell proliferation but not migration
Activation of platelet-derived growth factor (PDGF) receptors occurs through ligand-induced dimerization and autophosphorylation. In this study, we investigated the effects of mutation of tyrosine residue 857 (Y857) in the activation loop of the PDGF β-receptor (PDGFRβ) to phenylalanine (Y857F). In agreement with previous observations, we found that PDGFRβY857F had a severely diminished in vitro kinase activity. However, in vivo the overall amount of tyrosine phosphorylation of PDGFRβY857F was similar to that of the wild-type receptor, except for the tyrosine residue 771 (Y771) which displayed a stronger phosphorylation in the mutant receptor. Analysis of the ability to induce signal transduction revealed that the PDGFRβY857F mutant had an attenuated activation of Akt and Erk1/2 MAP kinase. In contrast, the mutant receptor efficiently mediated phosphorylation of the ubiquitin-ligase c-Cbl that participates in receptor internalization and degradation, and PLCγ which has previously been shown to be connected with various cellular responses, including migration. However, the protein tyrosine phosphatase SHP-2, implicated in the PDGF-induced mitogenic response, together with the adaptor proteins Alix and Stam, involved in intracellular sorting of receptor, was not phosphorylated in cells expressing PDGFRβY857F. We found that both receptor variants were internalized from the cell surface and degraded at a comparable rate. Interestingly, PDGFRβY857F was unable to mediate PDGF-BB-induced mitogenic signaling, whereas it could elicit a chemotactic response. 相似文献
14.
Gordon Parry Debble Farson Betsey Cullen Mina J. Bissell 《In vitro cellular & developmental biology. Plant》1988,24(12):1217-1222
Summary Primary cultures of mouse mammary epithelial cells synthesize significant quantities of chondroitin and heparan sulfate proteoglycans
(16). Long term treatment of such cultures with p-nitrophenyl-β-D-xylopyranoside leads to a 10–20 fold increase in the synthesis
and secretion of free chondroitin sulfate glycosaminoglycan (GAG) chains and assembly of a cell-associated matrix that is
relatively enriched in heparan sulfate proteoglycan.
This modulation of cell-synthesized proteoglycans leads to significant changes in cell morphology and cellular differentiation.
Notably cells cultured on plastic culture dishes change from being flattened to cuboidal. The synthesis of the milk proteins
α1, α2, and β-casein is also increases as is the formation of fat droplets and fat droplet membrane components. Promotion
of differentiation increases with increasing xyloside concentration in the range 0–1.5 mM, but there may be a block in secretion
at higher xyloside concentrations.
While the detailed mechanisms remain to be elucidated, we conclude that the composition of proteoglycans incorporated into
the matrix (and possibly the glycosaminoglycans secreted into the medium), may play a significant role in maintaining the
phenotypic characteristics of terminally differentiated mammary epithelial cells.
This research was supported by the Office of Health and Environmental Research, Office of Energy Research, U.S. Dept. of Energy
under contract No. DEAC-03-76SF00098 and by National Institutes of Health Grant CA44398-01 (G. Parry)
Editor's Statement Exogenous elements of extracellular matrix affect expression of cultured mammary cell function. This work
reports manipulation of cell-derived endogenous matrix elements and shows correlative changes in cell functions. 相似文献
15.
Hesling C Fattet L Teyre G Jury D Gonzalo P Lopez J Vanbelle C Morel AP Gillet G Mikaelian I Rimokh R 《EMBO reports》2011,12(7):665-672
TGF-β is a potent inducer of epithelial-to-mesenchymal transition (EMT), a process involved in tumour invasion. TIF1γ participates in TGF-β signalling. To understand the role of TIF1γ in TGF-β signalling and its requirement for EMT, we analysed the TGF-β1 response of human mammary epithelial cell lines. A strong EMT increase was observed in TIF1γ-silenced cells after TGF-β1 treatment, whereas Smad4 inactivation completely blocked this process. Accordingly, the functions of several TIF1γ target genes can be linked to EMT, as shown by microarray analysis. As a negative regulator of Smad4, TIF1γ could be crucial for the regulation of TGF-β signalling. Furthermore, TIF1γ binds to and represses the plasminogen activator inhibitor 1 promoter, demonstrating a direct role of TIF1γ in TGF-β-dependent gene expression. This study shows the molecular relationship between TIF1γ and Smad4 in TGF-β signalling and EMT. 相似文献
16.
Cui YM Wang H Liu QR Han M Lu Y Zhao CQ 《Bioorganic & medicinal chemistry letters》2011,21(15):4400-4403
Two new flavans (1, 2) and a new flavanone (3), together with three known compounds (4-6), were isolated from the roots of Iris tenuifolia. Their structures were elucidated by means of spectroscopic methods including 1D and 2D NMR techniques and mass spectrometry. Compounds 1, 4, and 6 were further confirmed by single-crystal X-ray diffraction analysis. Biological evaluation showed that compounds 1 and 4 were positive in inhibiting β-amyloid (Aβ) aggregation and promoting neural stem cells (NSCs) proliferation, respectively. 相似文献
17.
《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1986,887(2):150-156
The adenylate cyclase activator, forskolin, was found to induce expression of class I and class II major histocompatibility complex antigens in a B precursor cell line, Reh, as well as in a B lymphoid cell line, Raji. No such effect was, however, observed when the promyelocytic cells line HL-60 was treated with either forskolin or the cAMP analogue 8-bromoadenosine cyclic monophosphate. As expected, all three cell lines showed reduced proliferation upon forskolin treatment. Forskolin induced expression of class I and class II major histocompatibility complex antigens in cell lines not affected by interferon-γ and vice versa, indicating that cAMP is not involved in the regulation of histocompatibility antigens by interferon-γ. We also compared the effect of interferon-γ and 12-O-tetradecanoylphorbol 13-acetate on major histocompatibility complex class I and class II expression, and despite differences in the response on the tested cell lines, we can not at this point exclude the possibility that protein kinase C is involved in the action of interferon-γ. 相似文献
18.
Ewa Pocheć Marcelina Janik Dorota Hoja-ŁukowiczPaweł Link-Lenczowski Małgorzata PrzybyłoAnna Lityńska 《European journal of cell biology》2013
Acquisition of metastatic potential is accompanied by changes in cell surface N-glycosylation. One of the best-studied changes is increased expression of N-acetylglucosaminyltransferase V enzyme (GnT-V) and its products, β1,6-branched N-linked oligosaccharides, observed in the tumorigenesis of many cancers. In this study we demonstrate that during the transition from the vertical growth phase (VGP) (WM793 cell line) to the metastatic stage (WM1205Lu line), β1,6 glycosylation of melanoma cell surface proteins increases as a consequence of elevated expression of the GnT-V-encoding Mgat-5 gene. Treatment with swainsonine led to reduced cell motility on fibronectin in both cell lines; the effect was stronger in metastatic cells, probably due to the higher content of GlcNAc β1,6-branched glycans on the main fibronectin receptors – integrins α5β1 and α3β1. Our results show that GlcNAc β1,6 N-glycosylation of cell surface receptors, which increases with the aggressiveness of melanoma cells, is an important factor influencing melanoma cell migration. 相似文献
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Somjen D Katzburg S Sharon O Grafi-Cohen M Knoll E Stern N 《Journal of cellular biochemistry》2011,112(2):625-632
In cultured human osteoblasts estradiol-17β (E2) modulated DNA synthesis, the specific activity of creatine kinase BB (CK), 12 and 15 lipoxygenase (LO) mRNA expression and formation of 12- and 15-hydroxyeicosatetraenoic acid (HETE). We now investigate the response of human bone cell line (SaOS2) to phytoestrogens and estrogen receptors (ER)-specific agonists and antagonists. Treatment of SaSO2 with E2, 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; ERβ-specific agonist), 4,4',4″-[4-propyl-(1H)-pyrazol-1,3,5-triyl] tris-phenol (PPT; ERα-specific agonist), biochainin A (BA), daidzein (D), genistein (G) and raloxifene (Ral) showed increased DNA synthesis and CK. Ral inhibited completely all stimulations except DPN and to some extent D. The ERα-specific antagonist methyl-piperidino-pyrazole (MPP) and the ERβ-specific antagonist 4-[2-phenyl-5,7-bis (tri-fluoro-methyl) pyrazolo [1,5-a]pyrimidin-3-yl] phenol (PTHPP) inhibited DNA synthesis, CK and reactive oxygen species (ROS) formation induced by estrogens according to their receptors affinity. The LO inhibitor baicaleine inhibited only E2, DPN and G's effects. E2 and Ral unlike all other compounds had no effect on ERα mRNA expression, while ERβ mRNA expression was stimulated by all compounds. All compounds modulated the expression of 12LO and 15LO mRNA, except E2, PPT and Ral for 12LO, and 12- and 15-HETE productions and stimulated ROS formation which was inhibited by NADPH oxidase inhibitors diphenyleneiodonium chloride (DPI) and N-acetyl cysteine and the estrogen inhibitor ICI. DPI did not affect hormonal-induced DNA and CK. In conclusion, we provide evidence for the separation of mediation via ERα and ERβ pathways in the effects of estrogenic compounds on osteoblasts, but the role of LO/HETE/ROS is unclear. 相似文献