bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions between growth factor receptors and corresponding monoclonal antibodies in human tumors
Authors: Rodeck Ulrich , Herlyn Meenhard , Koprowski Hilary 
Published: December 2004

AbstractMonoclonal antibodies (MAbs) to the human epidermal growth factor (EOF) receptor, the type I insulin‐like growth factor (IGF) receptor, and the nerve growth factor (NGF) receptor were used to study the growth regulation of malignant cells. Anti‐EGF receptor MAb 425 inhibited the growth of A 431 squamous carcinoma cells which express high numbers of EGF receptors on their surfaces. Growth inhibition induced by MAb 425 was accompanied by alterations of the cell‐cycle distribution of these cells, indicating the ability of a monoclonal antibody to act as a biologically active ligand. Growth stimulation of melanoma cells by EGF was unrelated to EGF receptor expression on the cell surface. Insulin‐and IGF‐I‐induced growth stimulation of melanoma cells was inhibited by MAb α‐3 which reacts with the type I IGF receptor. This result indicates that the type I IGF receptor mediated growth stimulation not only by IGF‐I but also by insulin. Normal melanocytes and cells of all stages of tumor progression expressed in tissue culture the receptor for NGF, but no effect on the growth of these cells has been observed.
Human teratocarcinoma stem cells: Glycolipid antigen expression and modulation during differentiation
Authors: Andrews Peter W. 
Published: December 2004

AbstractTeratocarcinomas are germ cell tumors in which pluripotent stem cells, embryonal carcinoma (EC) cells, undergo differentiation along the pathways resembling those occurring during early embryogenesis. Human EC cell lines established in vitro provide a model for studying embryonic cellular differentiation in a way that is pertinent to early human development. The predominant glycolipid antigens expressd by EC cells of both humans and mice have globoseries core structures; in humans they are terminally modified to yield the monoclonal antibody‐defined stage‐specific embryonic antigens SSEA‐3 and SSEA‐4, and also globo‐ABH antigens; in the mouse terminal modification yields the Forssman antigen rather than SSEA‐3 and ‐4. These observations focus attention on the possible role of the P‐blood group system, which regulates synthesis of globoseries oligosaccharides, in the behavior of cells in the early embryo and in teratocarcinomas. Marked changes in the core structures of the cell surface glycolipids occur as the EC cells differentiate; thus globoseries structures rapidly diminish and are replaced by lactoseries and then by ganglioseries glycolipids. During differentiation of the NTERA‐2 line of pluripotent human EC cells into neurons and other cell types, the various subsets of differentiated cells that arise are distinguished by their differential expression of new glycolipid antigens, particularly ganglioside GT3 (recognized by antibody A2B5), and ganglioside 9‐0‐acetyl GD3 (recognized by antibody ME311). Neurons are found among the A2B5+/ME311− cells.
Melanoma growth stimulatory activity: Isolation from human melanoma tumors and characterization of tissue distribution
Authors: Richmond Ann , Thomas H. Greg 
Published: December 2004

AbstractMelanoma growth stimulatory activity (MGSA) is an acid and heat stable, autostimulatory growth factor which was first isolated from culture medium conditioned by the Hs294T human melanoma cell line. In this report, we describe the purification of MGSA from acid ethanol extracts of Hs294T tumors grown in nude mice using a series of Bio‐Gel P30, reverse phase‐high performance liquid chromatography and heparin‐sepharose steps. This modified procedure provides a 10‐fold improved yield of MGSA over previously published procedures. Purified MGSA‐stimulated melanoma cell growth in both 3H‐thymidine and cell number assays over a concentration range of 0.06 to 6 ng/ml. The MGSA bioactivity was primarily associated with fractions which exhibited molecular weights of 16 and 13–14 Kd based upon sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Purified platelet‐derived growth factor (PDGF), insulin‐like growth factor (IGF‐1), transforming growth factor‐beta (TGFβ), and epidermal growth factor (EGF) in combination with TGFβ did not stimulate 3H‐thymidine incorporation in Hs294T cells under the conditions used for MGSA bioassay. Monoclonal antibody to MGSA was used to screen melanoma and benign nevus cultures as well as fixed sectioned tissue for MGSA. The majority of the melanoma cultures were MGSA positive, while most nevus cultures were MGSA negative. However, when fixed sectioned tissue was screened for MGSA immunoreactivity, melanoma tissue was MGSA positive and three‐fourths of the benign nevi were MGSA positive. In addition, epidermal keratinocytes and several tissues exhibiting proliferative disorders contained immunoreactive MGSA. These data suggest that MGSA may be a normal regulator of growth and that the microenvironment of the cell may regulate both production of MGSA and response to MGSA.
Effects of fibroblasts and endothelial cells on inactivation of target proteases by protease nexin‐1, heparin cofactor II, and C1‐inhibitor
Authors: Hiramoto Sheree A. , Cunningham Dennis D. 
Published: December 2004

AbstractPrevious studies have shown that glycosaminoglycans in the extracellular matrix accelerate the inactivation of target proteases by certain protease inhibitors. It has been suggested that the ability of the matrix of certain cells to accelerate some inhibitors but not others might reflect the site of action of the inhibitors. Previous studies showed that fibroblasts accelerate the inactivation of thrombin by protease nexin‐1, an inhibitor that appears to function at the surface of cells in extravascular tissues. The present experiments showed that endothelial cells also accelerate this reaction. The accelerative activity was accounted for by the extracellular matrix and was mostly due to heparan sulfate. Fibroblasts but not endothelial cells accelerated the inactivation of thrombin by heparin cofactor II, an abundant inhibitor in plasma. This is consistent with previous suggestions that heparin cofactor II inactivates thrombin when plasma is exposed to fibroblasts and smooth muscle cells. Neither fibroblasts nor endothelial cells accelerated the inactivation of C1s by plasma C1‐inhibitor.
Modulation of the epidermal growth factor receptor by brain‐derived growth factor in Swiss mouse 3T3 cells
Authors: Huang Shuan Shian , Lokeshwar Vinata B. , Huang Jung San 
Published: December 2004

AbstractIncubation of Swiss mouse 3T3 cells at 37°C with bovine brain‐derived growth factor (BDGF) decreased the cell surface 125I‐EGF binding activity of these cells by 70–80%. This down‐modulation of the EOF receptor by BDGF was time, temperature, and dose dependent Scatchard plot analysis indicated that BDGF binding led to a selective decrease in the number of high‐affinity EGF receptors. The BDGF‐induced down‐modulation of the EGF receptor was completely blocked by protamine, a potent inhibitor of receptor binding and mitogenic activities of BDGF.BDGF down‐modulated the EGF receptor in phorbol myristic acetate (PMA)‐pretreated cells, as well as in control cells. Furthermore, PMA‐pretreated cells responded mitogenically to BDGF, whereas PMA itself failed to stimulate the mitogenic response of PMA‐pretreated cells. This BDGF‐induced down‐modulation of the EGF receptor in PMA‐desensitized cells suggests that BDGF down‐regulates the EGF receptor by a mechanism distinct from that of PMA.Incubation of cells with compounds which are known to inhibit pinocytosis blocked the down‐modulation induced either by BDGF or by platelet‐derived growth factor (PDGF) but had no effect on the PMA‐induced down‐modulation. Incubation of cells with inhibitors of receptor recycling enhanced the BDGF‐induced down‐modulation of the EGF receptor. These results suggest that BDGF and PDGF induce down‐modulation of the EGF receptor by increasing the internalization of cell surface high‐affinity receptors and that the internalization process may not be required for down‐modulation induced by PMA.
Mechanism of induction of class I major histocompatibility antigen expression by murine leukemia virus
Authors: Faller Douglas V. , Wilson Lise D. , Flyer David C. 
Published: December 2004

AbstractAlterations in expression of major histocompatibility complex (MHC) antigens on tumor cells clearly correlate with the tumorgenicity and metastatic potential of those cells. These changes in the biological behavior of the tumor cells are presumably secondary to resulting changes in their susceptibility to immune recognition and destruction. Murine leukemia viruses (MuLV) exert regulatory effects on class I genes of the MHC locus. MuLV infection results in substantial increases in cell surface expression of all three class I MHC antigens. These viral effects on MHC antigen expression profoundly influence immune‐mediated interaction with the infected cells, as assessed by cytotoxic T lymphocyte recognition and killing. Control of class I MHC and beta‐2 microglobulin genes by MuLV takes place via a trans‐acting molecular mechanism. MuLV controls expression of widely separated endogenous cellular MHC genes, transfected xenogeneic class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to a bacterial reporter gene. These findings indicate that MuLV exerts its effects on MHC expression via a trans mechanism. The MuLV‐responsive sequences on the MHC genes appear to lie within 1.2 kilobases upstream of the initiation codon for those genes.
Phosphorylation of ankyrin down‐regulates its cooperative interaction with spectrin and protein 3
Authors: Cianci Carol D. , Giorgi Mauro , Morrow Jon S. 
Published: December 2004

AbstractAnkyrin mediates the primary attachment between beta spectrin and protein 3. Ankyrin and spectrin interact in a positively cooperative fashion such that ankyrin binding increases the extent of spectrin tetramer and oligomer formation (Giorgi and Morrow: submitted, 1988). This cooperative interaction is enhanced by the cytoplasmic domain of protein 3, which is prepared as a 45–4l‐kDa fragment generated by chymotryptic digestion of erythrocyte membranes. Using sensitive isotope‐ratio methods and non‐denaturing PAGE, we now demonstrate directly (1) the enhanced affinity of ankyrin for spectrin oligomers compared to spectrin dimers; (2) a selective stimulation of the affinity of ankyrin for spectrin oligomer by the 43‐kDa cytoplasmic domain of protein 3; and (3) a selective reduction in the affinity of ankyrin for spectrin tetramer and oligomer after its phosphorylation by the erythrocyte cAMP‐independent membrane kinase. The phosphorylation of ankyrin does not affect its binding to spectrin dimer. Ankyrin also enhances the rate of interconversion between dimer‐tetramer‐oligomer by 2–3‐fold at 30°C, and in the presence of the 43‐kDa fragment, ankyrin stimulates the rate of oligomer interconversions by nearly 40‐fold at this temperature. These results demonstrate a long‐range cooperative interaction between an integral membrane protein and the peripheral cytoskeleton and indicate that this linkage may be regulated by covalent protein phosphorylation. Such interactions may be of general importance in nonerythroid cells.
Caldesmon: A common actin‐linked regulatory protein in the smooth muscle and nonmuscle contractile system
Authors: Sobue Kenji , Kanda Keiko , Tanaka Toshihiko , Ueki Noboru 
Published: December 2004

AbstractCaldesmon was originally purified from gizzard smooth muscle as a major calmo‐dulin‐binding protein which also interacts with actin filaments. It has an alternative binding ability to either calmodulin or actin filaments depending upon the concentration of Ca2+(“flip‐flop binding”). Two forms of caldesmon (Mr's in the range of 120–150 kDa and 70–80 kDa) have been demonstrated in a wide variety of smooth muscles and nonmuscle cells. Immunohistochemical studies suggest that caldesmon is colocalized with actin filaments in vivo. Considering its abundance, the Ca2+ ‐dependent flip‐flop binding ability to either calmodulin or actin filaments, and its intracellular localization, caldesmon is expected to be involved in contractile events. Recent results from our laboratory have led to the conclusion that caldesmon regulates the smooth muscle and nonmuscle actin‐myosin interaction and the smooth muscle actin‐high Mr actin‐binding protein (ABP or filamin) interactin in a flip‐flop manner. It might function in cell motility by regulating the contractile system.
Effect of transforming growth factor‐α on inositol phospholipid metabolism in human epidermoid carcinoma cells
Authors: Kato Miwako , Takenawa Tadaomi , Twardzik Daniel R. 
Published: December 2004

AbstractTransforming growth factor‐α (TGF‐α) stimulates (in a dose‐dependent manner) the incorporation of [32P]Pi into phosphatidylinositol(PI), phosphatidylinositol 4‐phosphate (PIP), phosphatidylinositol 4,5‐bisphosphate (PIP2), and phosphatidic acid (PA) in the human epidermoid carcinoma cell line (A431). The effect of TGF‐α on the incorporation was found to be similar to that of EGF. On the other hand, a striking difference in the activation of diacylglycerol (DG) kinase activity was seen between TGF‐α and EGF. At least 100 times more TGF‐α was required to achieve maximal stimulation of DG kinase activity relative to EGF. These results suggest that the activation of DG kinase by TGF‐α may involve a mechanism independent from or subsequent to activation of the EGF receptor.
Structure and expression of Ick transcripts in human lymphoid cells
Authors: Perlmutter Roger M. , Marth Jamey D. , Lewis David B. , Peet Richard , Ziegler Steven F. , Wilson Christopher B. 
Published: December 2004

AbstractThe murine Ick gene encodes a membrane‐associated protein tyrosine kinase that has been implicated in lymphocyte oncogenesis. Here we report the structure of normal human Ick transcripts and the pattern of expression of these transcripts in developing thymus and in peripheral T cell subsets. The human Ick gene encodes a 509 amino acid polypeptide that is closely related to the murine Ickencoded protein throughout its length. Analysis of the deduced amino acid sequence of human p56Ick demonstrates that an amino‐terminal domain, widely divergent among the seven known src family members, has been conserved between murine and human p56Ick, and thus probably includes sequences crucial to the lymphocyte‐specific function of this molecule. Human Ick transcripts were detected in CD4+ and CD8+ T cells, in partially purified B cells, and in Epstein‐Barr virus‐immortalized B cell lines, but not in monocytes, granulocytes, or in nonhematopoietic cell types. Human Ick transcripts are readily detectable in fetal thymocytes at 70 days of gestation, but not at 57 days of gestation, indicating that Ick expression appears coordinately with the appearance of lymphoid cells in the developing thymus. Thus Ick gene expression is a marker for cells of the lymphocyte lineage in man. We conclude that the Ick gene probably participates in a signal transduction pathway uniquely present in lymphoid cells.
Cyclin mRNA and protein expression in recombinant interleukin 2‐stimulated cloned murine T lymphocytes
Authors: Shipman P. M. , Sabath D. E. , Fischer A. H. , Comber P. G. , Sullivan K. , Tan E. M. , Prystowsky M. B. 
Published: December 2004

AbstractExpression of cyclin, a non‐histone nuclear protein, during recombinant interleukin 2 (rIL2)‐driven cell‐cycle progression of cloned T lymphocytes has been assessed. We found that expression of cyclin protein, as detected by immunofluorescence, is tightly associated with proliferation, and not merely S‐phase, of L2 cells stimulated with rIL2. Cyclin immunofluorescence was detected in all cell‐cycle phases (G1/S/G2/M, as detected by flow cytometry) of proliferating L2 cells. Accumulation of cyclin mRNA levels was induced as early as 1 h after stimulation, was maximal at 25–49 h, and remained elevated throughout stimulation, as detected by Northern blot analysis. A cDNA‐encoding murine cyclin was cloned from a cDNA library prepared from IL2‐stimulated cloned T cells. The sequence of the 5′ end of the murine cyclin cDNA was determined and found to be 88% and 82% similar to the sequences of cDNA clones encoding rat and human cyclin, respectively. The present studies demonstrate that cyclin protein and mRNA accumulation are highly regulated during IL2‐induced proliferation of a cloned T cell. These data provide a framework for addressing the molecular mechanisms regulating cyclin gene expression during cellular proliferation.
A polypeptide growth inhibitor isolated from lactating bovine mammary gland (MDGI) is a lipid‐carrying protein
Authors: Böhmer Frank‐D. , Mieth Maren , Reichmann Gunter , Taube Christel , Grosse Richard , Hollenberg Morley D. 
Published: December 2004

AbstractMammary‐derived growth inhibitor (MDGI), a polypeptide growth inhibitor isolated from lactating bovine mammary tissue, previously shown to have extensive sequence homology with fatty acid‐binding proteins, was demonstrated to meet the criteria of a fatty acid‐binding protein. The protein was found to bind [3H]palmitic acid in a saturable manner and to be complexed with endogeneous free fatty acids. [3H]palmitic acid, when bound to the protein, was more rapidly taken up by the target cells (human mammary carcinoma cells [MaTu]) than was free [3H]palmitic acid, suggesting a lipid carrier function for the inhibitor. It is suggested that the fatty acid‐binding properties of MDGI may relate to its ability to inhibit cell growth in vitro and to regulate other cellular functions.
Retroviruses expressing different levels of the normal epidermal growth factor receptor: Biological properties and new bioassay
Authors: Velu Thierry J. , Beguinot Laura , Vass William C. , Zhang Ke , Pastan Ira , Lowy Douglas R. 
Published: December 2004

AbstractTwo retroviral DNAs that encode the normal human epidermal growth factor (EGF) receptor hEGFR have been generated by inserting a hEGFR cDNA into two different retroviral vectors. One DNA (pCO11‐EGFR‐neo) also contained a linked selectable marker gene (neoR). The other (pCO12‐EGFR) only expresses hEGFR. When introduced into NIH3T3 cells, the two DNAs and the viruses derived from them induced a fully transformed phenotype, including focal transformation and growth in agar or low serum, but transformation depended entirely upon EGF being present in the growth medium. Compared with pCO11‐EGFR‐neo, pCO12‐EGFR induced EGF‐dependent transformation 2–5 times more efficiently and expressed higher numbers of receptors (4 × 105 vs. 1 × 105 EGF receptors per cell). The results indicate that transforming potential is directly related to the number of EGF receptors. In defined, serum‐free medium that contained only very low concentrations of insulin (0.6 μg/ml) and transferrin (0.6 μg/ml), hEGFR‐virus infected cells were able to grow with EGF as the only growth factor. Moreover, daily incubation of the cells with EGF for only 30 min was sufficient to induce growth. NR6 cells, which lack endogenous EGF receptors, were transformed as efficiently as NIH3T3 cells by the hEGFR virus. The dose‐dependent growth response to EGF of infected NR6 cells grown in serum‐free medium can be used as a highly sensitive bioassay for the quantitative assessment of EGF and transforming growth factor type α (TGFα). This bioassay is at least as sensitive as previously reported radioimmunoassays and can measure a much wider concentration range (10 pg–100 ng/ml). Uninfected NR6 cells or NR6 cells infected by helper virus alone can be used as controls for the EGF specificity of growth stimulation.
Does the lack of regression‐associated mRNA expression render a rat ventral prostate epithelial cell line androgen independent?
Authors: Montpetit Michael L. , Tenniswood Martin P. 
Published: December 2004

AbstractA series of rapidly dividing epithelial (RDE) cell lines have been isolated from primary cultures of rat ventral prostate (RVP) epithelial cells. Unlike androgen‐dependent secretory epithelial cells, the RDE cells in culture do not express the androgen‐dependent secretory proteins, nor do they express the androgen‐repressed cell death sequences (TRPM‐2) found in the epithelial cells during prostatic regression. Screening of a cDNA clone library established from RDE cell mRNA has yielded a number of RDE cell‐specific sequences. One of these, RDE‐.25 is a 250‐base mRNA. The sequence of RDE‐.25 shows considerable homology with the rat growth hormone gene and two murine oncogene sequences. We believe that the absence of androgen‐repressed cell death sequence expression confers androgen independence for survival and growth, while the expression of RDE‐.25 may represent an autocrine growth stimulus which greatly increases the rate of cell division in these cells.
Phorbol diester enhances calcium ionophore A23187‐induced [3H]acetate incorporation into platelet‐activating factor in murine macrophages: Predominant incorporation into 1‐O‐acyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine
Authors: Wey Howard E. 
Published: December 2004

AbstractPretreatment of macrophages with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) has been shown to enhance the release of arachidonic acid from cell phospholipids in response to agonist stimulation. This study describes the ability of TPA to also alter calcium ionophore A23187‐induced incorporation of [3H]acetate into platelet activating factor (PAF). Cultured murine peritoneal macrophages were preincubated with [3H]acetate (25 μCi) and TPA (10 ng/ml) for 10 min, and subsequently incubated with 0.1 μM A23187 for 0.5–10 min. Buffer and cells were then extracted and PAF resolved by normal‐phase HPLC. Sequential exposure to TPA and A23187 resulted in a greatly enhanced incorporation (11,861 dpm/106 cells) of [3H]acetate into PAF compared to TPA alone, which did not significantly influence [3H]acetate incorporation into PAF, and 0.1 μM A23187, which induced minimal incorporation (688 dpm/106 cells). Macrophage‐produced [3H]PAF was resolved by HPLC, extracted, treated with phospholipase‐C, and acetylated to facilitate quantitation of 1‐O‐alkyl‐2‐acetyl‐GPC (PAF) from 1‐O‐acyl‐2‐acetyl‐GPC (acylPAF). A23187 alone (1 μM) produced 72% 1‐O‐acyl‐2‐[3H]acetyl‐GPC, and A23187 (0.1 μM) following TPA pretreatment produced 81% 1‐O‐acyl‐2‐[3H]acetyl‐GPC. Less than 2% of the radioactivity of acylPAF was in the acyl moiety. These data support a role for protein kinase C in modulating agonist‐induced PAF synthesis. The results also suggest that acetyltransferase of murine macrophages does not possess specificity for 1‐O‐alkyl‐2‐lyso‐GPC, and that availability of specific species of lyso‐phospholipid may determine the type of PAF produced.