bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin‐like growth factor‐binding protein enhancement of insulin‐like growth factor‐i (IGF‐I)–mediated DNA synthesis and IGF‐I binding in a human breast carcinoma cell line
Authors: Chen Jian‐Chyi , Shao Zhi‐Ming , Sheikh M. Saeed , Hussain Arif , Leroith Derek , Roberts Charles T. , Fontana Joseph A. 
Published: February 2005

AbstractThe insulin‐like growth factors (IGFs) are potent mitogens for malignant cell proliferation. The majority of secreted IGFs are bound to specific IGF‐binding proteins (IGFBPs) that are secreted by a large number of cells. These proteins may either inhibit or enhance IGF actions. Breast carcinoma cells secrete a variety of IGFBPs. We have previously demonstrated that retinoic acid (RA) inhibition of IGF‐l– stimulated MCF‐7 cell proliferation is associated with increased IGFBP‐3 levels in the conditioned media. We therefore investigated the effect of recombinant IGFBP‐3 as well as IGFBP‐2, ‐4 and ‐5 on IGF‐l stimulation of DNA synthesis and IGF‐I binding in the MCF‐7 human breast carcinoma cell line. IGFBP‐2 and ‐3 enhanced IGF‐l stimulation of DNA synthesis in MCF‐7 cells while IGFBP‐4 and ‐5 had no effect. Transfection of MCF‐7 cells with an IGFBP‐3 expression vector resulted in the enhanced secretion of IGFBP‐3 with an accompanying increase in IGF‐l binding as well as increased cell proliferation upon treatment of the cells with IGF‐l. IGF‐l preincubation of MCF‐7 cells transfected with control pSVneo plasmids results in cells refractory to further IGF‐l stimulation of thymidine incorporation while IGF‐l continues to stimulate [3H]‐thymidine incorporation in IGFBP‐3–transfected MCF‐7 cells, suggesting that IGFBP‐3 protects the cells from IGF‐l–mediated down regulation of its receptor. Therefore, IGFBP‐3 secreted by MCF‐7 cells can enhance IGF‐l stimulation of DNA synthesis, increase IGF‐l binding to these cells, and prevent IGF‐l–induced desensitization of its own receptor, suggesting that IGFBP‐3 plays a significant role in IGF‐l–mediated breast carcinoma proliferation. © 1994 Wiley‐Liss, Inc.
Migratory interaction of amphibian epidermal cells with components of the basement membrane
Authors: Donaldson Donald J. , Mahan James T. , Tsilibary Effie C. , McCarthy James B. , Dixit Saryu N. , Chung Albert E. 
Published: February 2005

AbstractIn adult newts, basal epidermal cells adjacent to a fresh wound move toward the damaged area by migrating over the epidermal basement membrane. In an attempt to determine which basement membrane components mediate this migration, small pieces of glass coated with various natural matrices, purified proteins, or fragments of proteins were implanted into skin wounds such that epidermal cells attempting to form a wound epithelium would encounter the implants. Laminin derived from a cell line (M1536‐B3) that produces no type IV collagen was inactive as a migration substrate. Migration on recombinant entactin was somewhat better than on laminin but was still only ∼ 14% of that on type I collagen. M15 matrix, a laminin and entactin‐containing product of M1536‐B3 cells, was no better than entactin alone. Type IV collagen was an excellent substrate, producing slightly more migration than corresponding concentrations of type I collagen at nearly all concentrations tested. Migration on type IV lacking the NC1 domain was at least as good as on intact type IV. All the activity in type IV was present in a 95 kD fragment (al (IV)95) from the carboxy terminal two‐thirds of the α1 chain. Approximately 60% of the activity on β1(IV)95 was obtained on implants coated with a 110 amino acid fragment of the α1 chain derived from the carboxy terminal half of α1(IV)95. Adding the synthetic peptide, arg‐gly‐asp‐ser (RGDS) to the medium, biocked migration on fibronectin‐coated implants but had no effect on implants coated with type IV, suggesting that migration on type IV involves different cell surface receptors than those mediating migration over fibronectin. Matrigel, a commercial product containing most basement membrane components, was a poor migration substrate. Thus if type IV mediates basal cell migration toward a wound in vivo, there may have to be some alterations in basement membrane structure to allow epidermal receptors to access type IV active site(s). © 1994 Wiley‐Liss, Inc.
Increased ambient pressure stimulates proliferation and morphologic changes in cultured endothelial cells
Authors: Sumpio Bauer E. , Widmann Mark D. , Ricotta Joseph , Awolesi Mark A. , Watase Makoto 
Published: February 2005

AbstractVery little is known about the effects of pressure within the vascular system on EC phenotype. To study this, bovine aortic EC were seeded on rat type I collagen plates (2,000/cm2) and allowed to attach for 24 hours. The cells were exposed to either atmospheric, 40, 80, or 120 mm Hg pressure by placing them in a plexiglass pressure chamber loaded with 5% CO2/air and maintained at 37°C inside an incubator. Chamber pressure was continuously monitored with an amplified voltage transducer connected to a digital monitor. EC were maintained in DMEM supplemented with 10% calf serum and substrates for up to 9 days. The results indicate that EC proliferation is influenced by their ambient pressure. EC subjected in vitro to pressures comparable to mean systemic blood pressures had a significant increase in cell number compared to EC exposed to atmospheric pressures. EC were elongated and appeared to align randomly. We hypothesize that the systemic pressure which the endothelium is exposed to in vivo may have a significant regulatory influence on the ability of the endothelium to proliferate which may affect the endothelial cell response to injury. © 1994 Wiley‐Liss, Inc.
Upregulation of IGF1, IGF1‐receptor, and late growth related genes in ventricular myocytes acutely after infarction in rats
Authors: Reiss Krzysztof , Meggs Leonard G. , Li Peng , Olivetti Giorgio , Capasso Joseph M. , Anversa Piero 
Published: February 2005

AbstractTo determine the effects of acute myocardial infarction on the expression of insulin‐like growth factor1 (IGF1) and insulin‐like growth factor1 receptors (IGF‐1R) on the surviving myocytes of the left and right ventricles, large infarcts were produced in rats and the animals sacrificed 2 days later. Hemodynamic measurements of left and right ventricular pressures, +dP/dt and ‐dP/dt, and central venous pressure documented that coronary occlusion was associated with a severe impairment of cardiac function. By employing reverse transcriptase polymerase chain reaction (RTPCR), a low level of expression of IGF‐1R mRNA was detected in myocytes from sham‐operated rats. Acute myocardial infarction was found to enhance by nearly twofold the message for IGF‐1R in viable myocytes biventricularly. Moreover, IGF1 mRNA increased 4.3‐fold and 9.4‐fold in left and right myocytes, respectively. In order to establish whether the upregulation of IGF1 and IGF‐1R with infarction was coupled with induction of late growth related genes, which are known to be implicated in DNA replication and mitotic division, proliferating cell nuclear antigen (PCNA) and histone‐H3 expression was assessed by Northern blot and RTPCR. The level of expression of PCNA mRNA was found to be increased 3.9‐fold and 2.4‐fold in left and right myocytes, respectively, from infarcted hearts. Corresponding increments in histone‐H3 mRNA were 25.5‐fold and 5.3‐fold, respectively. However, PCNA protein as detected by immunoperoxidase staining was restricted to a limited number of myocyte nuclei adjacent to the necrotic myocardium of the left ventricle. In conclusion, acute myocardial infarction is associated with enhanced expression of IGF1 and IGF‐1R on stressed myocytes, and this phenomenon may activate genes essential for DNA synthesis, possibly affecting myocyte growth. These processes may be fundamental for the reconstitution of tissue mass and amelioration of function after infarction. © 1994 Wiley‐Liss, Inc.
Alterations in the cyclic AMP signal transduction pathway regulating ribonucleotide reductase gene expression in malignant H‐ras transformed cell lines
Authors: Hurta Robert A. R. , Wright Jim A. 
Published: February 2005

AbstractRibonucleotide reductase is a highly regulated activity responsible for reducing ribonucleotides to deoxyribonucleotides, which are required for DNA synthesis and DNA repair. We have tested the hypothesis that malignant cell populations contain alterations in signal pathways important in controlling the expression of the two genes that code for ribonucleotide reductase, R1 and R2. A series of radiation and H‐ras transformed mouse 10T1/2 cell lines with increasing malignant potential were exposed to stimulators of cAMP synthesis (forskolin and cholera toxin), an inhibitor of cAMP degradation (3‐isobutyl‐1‐methylxanthine) and a biologically stable analogue of cAMP (8‐bromo‐cAMP). Dramatic elevations in the expression of the R1 and R2 genes at the message and protein levels were observed in malignant metastatic populations, which were not detected in the normal parental cell line or in cells capable of benign tumor formation. These changes in ribonucleotide reductase gene expression occurred without any detectable modifications in the rates of DNA synthesis, showing that they were regulated by a novel mechanism independent of the S phase of the cell cycle. Furthermore, studies with forskolin (a stimulator of the protein kinase A signal pathway) and the tumor promoter 12–0‐tetradecanoylphorbol‐13‐acetate (a stimulator of the protein kinase C signal pathway), alone or in combination, indicated that their effects on R1 and R2 gene expression in a highly malignant cell line were greater than when they were tested individually, suggesting that the two pathways modulating R1 and R2 gene expression can cooperate to regulate ribonucleotide reduction, and interestingly this can occur in a synergistic fashion. Also, a direct relationship between H‐ras expression and ribonucleotide reductase gene expression was observed; analysis of forskolin mediated elevations in R1 and R2 message levels closely correlated with the levels of H‐ras expression in the various cell lines. In total, these studies demonstrate that ribonucleotide reductase expression is controlled by a complex process, and malignant ras transformed cells contain alterations in the regulation of signal transduction pathways that lead to novel modifications in ribonucleotide reductase gene expression. This signal mechanism, which is aberrantly regulated in malignant cells, may be related to regulatory pathways involved in determining ribonucleotide reductase expression in a S phase independent manner during periods of DNA repair. © 1994 Wiley‐Liss, Inc.
Synthesis, degradation, and subcellular localization of proteins encoded by the primary response genes TIS7/PC4 and TIS21/PC3
Authors: Varnum Brian C. , Reddy Srinivasa T. , Koski Raymond A. , Herschman Harvey R. 
Published: February 2005

AbstractMurine TIS7 and TIS21 cDNAs were cloned from phorbol ester‐induced Swiss 3T3 cells. The cognate rat cDNAs. PC4 and PC3, were cloned from nerve growth factor (NGF)‐treated PC12 pheochromocytoma cells. The TIS7/PC4 and TIS21/PC3 primary response genes are rapidly and transiently induced in response to serum, phorbol esters, and polypeptide growth factors in quiescent Swiss 3T3 cells and by NGF and other ligands in PC12 cells. In both 3T3 and PC12 cells the appearance of the TIS21/PC3 message precedes that of TIS7/PC4 message following ligand stimulation, suggesting that the TIS21/PC3 protein is likely to be synthesized more rapidly than the TIS7/PC4 protein. Using antisera prepared against recombinant TIS21 and TIS7 proteins, we find that the TIS21/PC3 protein is, indeed, synthesized more rapidly than the TIS7/PC4 protein following stimulation in both 3T3 and PC12 cells. In addition, “pulse‐chase” experiments demonstrate that the TIS21/PC3 protein is degraded much more rapidly than the TIS7/PC4 protein. The sequences of the predicted PC3 and PC4 proteins have lead to the speculation that these two proteins may both be secreted from cells following stimulation. The PC4 protein is reported to have some sequence similarity to interferons. The TIS21/PC3 protein contains a presumptive leader sequence. Using our antisera to the recombinant proteins, however, we cannot detect secretion of radiolabelled TIS7/PC4 or TIS21/PC3 protein. Immunohistochemical and subcellular fractionation experiments suggest that the TIS7 protein is a membrane associated, non‐nuclear intracellular protein. The TIS21 protein, in contrast, is' a non‐nuclear, soluble intracellular protein. © 1994 Wiley‐Liss, Inc.
Murine temperature‐sensitive DNA polymerase α mutant displays a diminished capacity to stimulate DNA synthesis in senescent human fibroblast nuclei in heterokaryons at the nonpermissive condition
Authors: Pendergrass William R. , Saulewicz Anthony C. , Hanaoka Fumio , Norwood Thomas H. 
Published: February 2005

AbstractWe have investigated the capacity of a murine cell line with a temperature‐sensitive (ts) mutation in the DNA polymerase α (Pola) locus and a series of ts non‐Pola mutant cell lines from separate complementation groups to stimulate DNA synthesis, in senescent fibroblast nuclei in heterokaryons. In the Pola mutant × senescent heterodikaryons, both human and murine nuclei display significantly diminished levels of DNA synthesis at the restrictive temperature (39.5°C) as determined by [3H]thymidine labeling in autoradiographs. In contrast, all of the non‐Pola mutants, as well as the parental (wild‐type) murine cells, induced similar levels of DNA synthesis in both parental nuclei at the nonpermissive and permissive temperatures. Similarly, young human fibroblasts are also able to initiate DNA synthesis in heterokaryons with the ts Pola mutant at the two temperatures. In order to determine if complementation of the non‐Pola mutants requires induction of serum responsive factors in the senescent cells, fusion studies of similar design were conducted with young and old human fibroblasts incubated in low serum (0.2%) for 48 hr prior to and after cell fusion. Again, a diminished level of DNA synthesis was observed at 39.5°C in the Pola mutant x senescent cell heterokaryons. In these low‐serum studies, both parental nuclei in the Pola x young cell heterokaryons and the human nuclei in heterokaryons with one of the non‐Pola mutants (FT107) also displayed diminished levels of DNA synthetic activity. All of the other mutants are able to support similar levels of synthetic activity at both temperatures in the presence of reduced serum. The nature of the mutation in three of the non‐Pola lines has not been determined but, like the Pola mutant cells, are inhibited in the G1 phase of the cell cycle when incubated at the nonpermissive temperature (39.5°C). The fourth non‐Pola mutant line is known to have at least one ts mutation in the cdc2 gene and is inhibited in the G2 phase when exposed to 39.5°C. These results suggest that there may be a functional deficiency of pol α in senescent human fibroblasts, and this replication factor may be one of the rate‐limiting factors involved in loss of the capacity to initiate DNA synthesis in senescent cells. © 1994 Wiley‐Liss, Inc.
Requirement for receptor‐bound urokinase in plasmin‐dependent cellular conversion of latent TGF‐β to TGF‐β
Authors: Odekon Lale E. , Blasi Francesco , Rifkin Daniel B. 
Published: February 2005

AbstractThe role of receptor‐bound urokinase‐type plasminogen activator (uPA) in cellular activation of latent transforming growth factor‐beta (LTGF‐β) was investigated in a model system of mouse LB6 cells transfected with either a human uPA receptor cDNA (LhuPAR+). a human prouPA cDNA (LhuPA), or a control neomycinresistance cDNA (Lneo). When LhuPAR+ cells were co‐cultured with LhuPA cells, the plasmin‐dependent fibrinolytic activity generated was more than that observed in either homotypic cultures with fivefold greater number of LhuPA cells or co‐cultures containing LhuPA and Lneo cells instead of the LhuPAR+ cells. The preferential activation of TGF‐β by co‐cultures with the greatest plasmin‐generation potential, LhuPAR+ and LhuPA cells, was confirmed by three independent bioassays. In the first assay, a 48% decrease in PA activity, a measure of active TGF‐β production, was observed with BAE cells treated with conditioned medium (CM) from co‐cultures of LhuPA and LhuPAR+ cells. Inclusion of neutralizing antibodies to TGF‐β abrogated the inhibitory effect of CM on PA activity demonstrating that the inhibitory molecule was TGF‐β. Addition of the amino terminal fragment of uPA (ATF) or omission of plasminogen from co‐cultures blocked both the fibrinolytic activity and the generation of TGF‐β activity in the CM. In the second assay, CM from co‐cultures of LhuPA and LhuPAR+ cells inhibited the migration of BAE cells in a wound assay. Controls with anti‐TGF‐β IgG indicated that the inhibition was due to TGF‐β. In the third assay, proliferation of mink lung epithelial cells was inhibited by CM generated by co‐cultures of LhuPA and LhuPAR+ cells as compared to CM from the same cells cultured in the absence of plasminogen or to CM from a co‐culture of LhuPA with LhuPAR− cells. Excess mannose‐6‐phosphate (M6P) blocked the generation of TGF‐β as assayed by both the BAE migration and PA assays, presumably because it interfered with cellsurface localization of LTGF‐β. Additionally, small numbers of LhuPA and LhuPAR+ cells co‐cultured with BAE cells inhibited the BAE cell PA activity via the paracrine action of TGF‐β. These results support the conclusion that plasmindependent activation LTGF‐β by LB6 cells is promoted by the surface localization of uPA by its receptor. © 1994 Wiley‐Liss, Inc.
Role of serum in the developmental expression of alkaline phosphatase in MC3T3‐E1 osteoblasts
Authors: Yohay Daniel A. , Zhang Jian , Thrailkill Kathryn M. , Arthur John M. , Quarles L. Darryl 
Published: February 2005

AbstractMC3T3‐E1 cells in culture exhibit a temporal sequence of development similar to in vivo bone formation. To examine whether the developmental expression of the osteoblast phenotype depends on serum derived factors, we compared the timedependent expression of alkaline phosphatase (ALP)‐a marker of osteoblastic maturation‐ in MC3T3‐E1 cells grown in the presence of fetal bovine serum (FBS) or resin/charcoal‐stripped (AXC) serum. ALP was assessed by measuring enzyme activity, immunoblotting, and Northern analysis. Growth of MC3T3‐E1 cells in FBS resulted in the programmed upregulation of alkaline phosphatase (ALP) post‐proliferatively during osteoblast differentiation. In the presence of complete serum, actively proliferating cells during the initial culture period expressed low ALP levels consistent with their designation as pre‐osteoblasts, whereas postmitotic cultures upregulated ALP protein, message, and enzyme activity. In addition, undifferentiated early cultures of MC3T3‐E1 cells were refractory to forskolin (FSK) stimulation of ALP, but became forskolin responsive following prolonged culture in FBS containing media. In contrast, MC3T3‐E1 cells grown in AXC serum displayed limited growth and failed to show a time‐dependent increase in alkaline phosphatase. Neither the addition of IGF‐I to AXC serum to augment cell number or plating at high density restored the time‐dependent upregulation of alkaline phosphatase. Cells incubated in AXC serum for 14 days, however, though expressing low alkaline phosphatase levels, maintained the capacity to upregulate ALP after FBS re‐addition or forskolin activation of cAMP‐dependent pathways. Such time‐dependent acquisition of FSK responsiveness and serum stimulation of ALP expression only in mature osteoblasts indicate the possible presence of differentiation switches that impart competency for a subset of osteoblast developmental events that require complete serum for maximal expression. © 1994 Wiley‐Liss, Inc.
Noradrenergic modulation of albumin expression in growth‐stimulated adult rat hepatocytes in primary culture
Authors: Fabregat Isabel , De Juan Carmen , Roncero CÉSar , Benito Manuel 
Published: February 2005

AbstractSerum albumin is the most abundant protein synthesized by liver cells, and its production is a reliable indicator of the differentiated state of hepatocytes. We have recently shown that fetal rat hepatocytes cultured under proliferative conditions, i.e., in the presence of EGF, responded to glucagon and noradrenaline increasing albumin protein and mRNA levels (de Juan et al., 1992,. J. Cell. Physiol., 152:95–101). This effect was mimicked by agents that increase cyclic AMP levels. In this report, we show that in regenerating liver, noradrenaline modulation of albumin expression seems to be different. Hepatocytes from hepatectomized rats were cultured at low cell density and in the presence of EGF. Under these conditions, noradrenaline, which acted synergistically with EGF increasing DNA synthesis (de Juan et al., 1992. Exp. Cell. Res., 202:495–500), produced a decrease in albumin mRNA levels. This effect was dose‐dependent, being maximum at 1 μM noradrenaline. Noradrenergic effect seemed to be mediated by α‐receptors, because it was blocked by prazosin, but not by propranolol. Other Ca2+‐increasing agents, as vasopressin, angiotensin II, or ATP, did not produce any effect. However, albumin mRNA levels decreased when the cells were incubated in the presence of tetradecanoyl phorbol‐13‐acetate (TPA). In addition, noradrenergic modulation of albumin expression was blocked by staurosporine, a protein kinase inhibitor with relative specificity for protein kinase C. Thus we can conclude that the role of noradrenaline on the regulation of liver growth and differentiation changes from fetal to adult life. This change is probably due to its action on different receptors: β‐receptors in fetal hepatocytes and α1‐receptors in the adult liver. © 1994 Wiley‐Liss, Inc.
C‐terminal fragments of parathyroid hormone‐related protein, PTHrP‐(107‐111) and (107‐139), and the N‐terminal PTHrP‐(1‐40) fragment stimulate membrane‐associated protein kinase C activity in rat spleen lymphocytes
Authors: Whitfield James F. , Isaacs Richard J. , Chakravarthy Balu R. , Durkin Jon P. , Morley Paul , Neugebauer Witold , Williams Ross E. , Willick Gordon , Rixon Raymond H. 
Published: February 2005

AbstractMembrane‐associated protein kinase C (PKC) activity in lymphocytes freshly isolated from rat spleen was stimulated by the C‐terminal parathyroid hormonerelated protein fragments, PTHrP‐(107–111) and PTHrP‐(107–139), at concentrations from 10−3 to 104 pM. By contrast, the same concentrations of PTHrP‐(120–139), Without the 107–111 TRSAW (‐Thr‐Arg‐Ser‐Ala‐Trp‐) sequence of the other C terminal fragments, did not stimulate spleen lymphocyte PKC. Low concentrations of the N‐terminal PTHrP‐(1–40) fragment also stimulated membrane‐associated PKC activity in the spleen lymphocytes. These results suggest that PTHrP might be an important physiological regulator of the immune response. Published 1994 Wiley‐Liss, Inc.
Pinocytic stimulation in Dictyostelium discoideum by γ‐benzene hexachloride
Authors: Gayatri R. , Chatterjee S. 
Published: February 2005

AbstractPinocytic activity is greatly stimulated in γ‐BHC (gamma isomer of benzene hexachloride) treated, vegetative cells of Dictyostelium discoideum as measured by 14C sucrose or FITC‐dextran uptake. Transmission electron microscopic studies also reveal the presence of a greater number of pinosomal vesicles in the pesticide‐treated Dictyostelium amoebae. The enhanced pinocytic activity has been discussed in relation to lipophilic interactions of γ‐BHC with the hydrophobic cell surface and the observed changes in the cytoskeletal proteins of the treated cells. © 1994 Wiley‐Liss, Inc.