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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin is required for the binding of basic fibroblast growth factor (bFGF) to high-affinity receptors on cells deficient in cell surface heparan sulfate proteoglycan. So that this heparin requirement could be evaluated in the absence of other cell surface molecules, we designed a simple assay based on a genetically engineered soluble form of murine FGF receptor 1 (mFR1) tagged with placental alkaline phosphatase. Using this assay, we showed that FGF-receptor binding has an absolute requirement for heparin. By using a cytokine-dependent lymphoid cell line engineered to express mFR1, we also showed that FGF-induced mitogenic activity is heparin dependent. Furthermore, we tested a series of small heparin oligosaccharides of defined lengths for their abilities to support bFGF-receptor binding and biologic activity. We found that a heparin oligosaccharide with as few as eight sugar residues is sufficient to support these activities. We also demonstrated that heparin facilitates FGF dimerization, a property that may be important for receptor activation.
Mol Cell Biol 1992 Jan
PMID:Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells. 130 90

The human neuroblastoma cell line CHP100 provides a useful model system in which to study the molecular mechanisms of transcriptional regulation of the low-affinity nerve growth factor receptor (NGFR) gene during neuronal development. Basic fibroblast growth factor (bFGF) induced morphological changes in CHP100 cells, including flattening of cell bodies and neurite outgrowth. bFGF also increased p75NGFR immunoreactivity, as assessed by immunocytochemistry, and increased p75NGFR mRNA levels, as assessed by Northern (RNA) blot analysis. A chimeric gene consisting of 6.7 kb of the 5'-flanking region of the human NGFR gene linked to the chloramphenicol acetyltransferase gene was constructed. In stable transformants of CHP100 cells, 10 ng of bFGF per ml induced an eightfold increase in chloramphenicol acetyltransferase activity. These results indicate that upstream elements of the NGFR gene mediate transcriptional regulation by bFGF.
Mol Cell Biol 1992 May
PMID:Basic fibroblast growth factor enhances nerve growth factor receptor gene promoter activity in human neuroblastoma cell line CHP100. 131 50

The sensitive technique of mRNA phenotyping with the reverse transcription-polymerase chain reaction was employed to determine the patterns of gene expression for several growth factor ligand and receptor genes during bovine preimplantation development. Several thousand bovine embryos encompassing a developmental series from one-cell zygotes to hatched blastocysts were produced by the application of in vitro maturation, fertilization, and oviductal epithelial cell embryo coculture methods. Transcripts for transforming growth factor (TGF-alpha) and platelet-derived growth factor (PDGF-A) are detectable in all preimplantation bovine stages as observed in the mouse. Transcripts for TGF-beta 2 and insulin-like growth factor (IGF-II) and the receptors for PDGF-alpha, insulin, IGF-I, and IGF-II are also detectable throughout bovine preimplantation development, suggesting that these mRNAs are products of both the maternal and the embryonic genomes in the cow, whereas in the mouse they are present only following the activation of the embryonic genome at the two-cell stage. In contrast to the mouse embryo, IGF-I mRNA was detected within preimplantation bovine embryos. Basic fibroblast growth factor (bFGF) is a maternal message in the bovine embryo, since it is only detectable up until the eight-cell embryo stage. Bovine trophoblast protein (bTP) mRNA was detectable within day 8 bovine blastocysts. As was observed in the mouse, the transcripts for insulin, epidermal growth factor (EGF), or nerve growth factor (NGF) were not detectable in any bovine embryo stage. Analyses of this type should aid the development of a completely defined culture medium for the more efficient production of preimplantation bovine embryos.
Mol Reprod Dev 1992 Feb
PMID:Expression of growth factor ligand and receptor genes in the preimplantation bovine embryo. 131 55

Expression of the mouse beta-PDGF receptor by gene transfer confers PDGF-dependent and reversible neuronal differentiation of PC12 pheochromocytoma cells similar to that observed in response to NGF and basic FGF. A common property of the PDGF, NGF, and basic FGF-induced differentiation response is the requirement for constant exposure of cells to the growth factor. To test the hypothesis that a persistent level of growth factor receptor signaling is required for the maintenance of the neuronal phenotype, we examined the regulation of the serine/threonine-specific MAP kinases after either short- (10 min) or long-term (24 h) stimulation with growth factors. Mono Q FPLC resolved two peaks of growth factor-stimulated MAP kinase activity that coeluted with tyrosine phosphorylated 41- and 43-kDa polypeptides. MAP kinase activity was markedly stimulated (approximately 30-fold) within 5 min of exposure to several growth factors (PDGF, NGF, basic FGF, EGF, and IGF-I), but was persistently maintained at 10-fold above basal activity after 24 h only by the growth factors that also induce PC12 cell differentiation (PDGF, NGF, and basic FGF). Thus the beta-PDGF receptor is in a subset of tyrosine kinase-encoded growth factor receptors that are capable of maintaining continuous signals required for differentiation of PC12 cells. These signals include the constitutive activation of cytoplasmic serine/threonine protein kinases.
Mol Biol Cell 1992 May
PMID:The beta-PDGF receptor induces neuronal differentiation of PC12 cells. 131 43

Basic fibroblast growth factor (bFGF) is a broad spectrum mitogen for many cells of neuroectodermal origin, including glial cells. The human malignant glioblastoma cell line U87-MG expresses high steady state levels of the bFGF mRNA and contains abundant stores of biologically active bFGF protein. In the present study we have examined the contribution of endogenous bFGF to the autocrine growth of these cells. Using reverse transcription-polymerase chain reaction, U87-MG cells were shown to express the mRNAs for both bFGF and the bFGF receptor, confirming the existence of the basic requirements for an autocrine loop. Addition of 5 microM bFGF-specific antisense oligonucleotide to U87-MG cultures significantly inhibited the growth rate of these cells within 48 h and blocked proliferation beyond 2 days. The corresponding bFGF-specific sense oligonucleotide did not significantly inhibit cell proliferation over the course of these experiments. Similarly, antisense oligonucleotides significantly inhibited colony formation in soft agar, while the sense sequence was without effect. Western blotting with antihuman bFGF revealed that U87-MG cells synthesize three isoforms of bFGF, approximately 18, 23, and 25 kilodaltons (kDa) in size. The 23- and 25-kDa isoforms together comprise approximately 80% of the total cellular stores of bFGF. Antisense treatment for 4 days reduced the abundance of the 23- and 25-kDa isoforms by 64-74%, but had little effect on the 18-kDa isoform. The inhibitory effect of the antisense oligonucleotides on anchorage-dependent proliferation was reversed by the addition of recombinant 18-kDa human bFGF.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1992 Jun
PMID:Phosphorothioate antisense oligonucleotides against basic fibroblast growth factor inhibit anchorage-dependent and anchorage-independent growth of a malignant glioblastoma cell line. 132 55

Basic fibroblast growth factor (bFGF) is a trophic factor synthesized in the central nervous system (CNS), where it is believed to play a role in neuronal maintenance and repair. Little is known about the regulation of this growth factor in the CNS. To determine whether the expression of the bFGF gene in the brain of adult animals changes in response to alterations of neuronal activity, we examined bFGF mRNA levels in several brain regions of rats experiencing focally-evoked convulsive seizures. Seizures were induced by microinjecting bicuculline unilaterally into an epileptogenic site within the deep prepiriform cortex, area tempestas (AT). By 5 h after initiation of brief limbic motor seizures from AT, there was a four fold increase in the levels of bFGF mRNA in the entorhinal cortex, hippocampus and olfactory bulb, but not in the caudate-putamen. The maximal expression of bFGF mRNA was reached by 10 h after seizure onset. In the same animals, the mRNA encoding nerve growth factor (NGF) was increased in entorhinal cortex and hippocampus, but not in the olfactory bulb. Our results demonstrate that neuronal activity can influence bFGF expression in an anatomically selective fashion and that acute changes in bFGF can occur in the uninjured mature brain. The increase in bFGF expression in response to excessive activation of specific neuronal circuitry may represent an adaptive response to protect against potential injury in those circuits.
Brain Res Mol Brain Res 1992 Oct
PMID:Basic fibroblast growth factor mRNA increases in specific brain regions following convulsive seizures. 133 86

The effect and mechanism of action of basic fibroblast growth factor (bFGF) on testicular steroidogenesis were investigated using as a model primary cultures of purified porcine Leydig cells from immature intact animals. Basic FGF increased basal and human chorionic gonadotrophin (hCG)-induced testosterone accumulation (with an ED50 of 0.64 ng/ml bFGF, 35 pM) in the medium following a long-term treatment. The effects of bFGF (10 ng/ml, 72 h) were found at all hCG concentrations tested (0.001-1 ng/ml), the growth factor affecting the maximal steroidogenic capacity of the Leydig cells but not their sensitivity to the gonadotrophin. In this context, we have therefore investigated whether the stimulatory effect of bFGF on testosterone formation was related to an increase of the steroidogenic enzyme activities. The data obtained indicate that the growth factor did not affect the gonadotrophin action on the formation of delta 5-steroid hormone, namely dehydroepiandrosterone (DHEA) (evaluated in the presence of 10(-5) M WIN 24540, an inhibitor of 3 beta-hydroxysteroid dehydrogenase/isomerase). By contrast, bFGF (10 ng/ml, 72 h) was found to increase in a comparable manner the conversion of pregnenolone, DHEA and delta 4-androstenedione into testosterone, suggesting a stimulatory effect on 17 beta-hydroxysteroid dehydrogenase activity. Indeed, bFGF enhanced in a dose-dependent manner (ED50 = 39 pM) this enzyme activity evaluated through the conversion of delta 4-androstenedione to testosterone. These effects of bFGF on Leydig cell steroidogenic activity are probably exerted through specific membrane bFGF receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1992 Nov
PMID:Basic fibroblast growth factor enhances testosterone secretion in cultured porcine Leydig cells: site(s) of action. 133 22

Previous studies have shown that basic fibroblast growth factor (bFGF) can modulate basal and luteinizing hormone/human chorionic gonadotropin (LH/hCG)-stimulated Leydig cell functions. It has not been ascertained whether these actions are due to direct or indirect effects on Leydig cells. To resolve this question, a multi-step procedure was used to isolate highly-purified Leydig cells from immature rats. 125I-bFGF binding studies were performed on cultured cells. Scatchard analysis of the data indicated a single binding site with an apparent Kd of 82 pM and a binding capacity of approximately 2800 sites per cell. Both bFGF and acidic FGF similarly were effective in displacing 125I-bFGF, suggesting that the receptor binds both bFGF and aFGF. However, neither hCG, follicle-stimulating hormone (FSH), insulin, insulin-like growth factor-1 (IGF-1), prolactin, platelet-derived growth factor (PDGF) or epidermal growth factor (EGF) were effective competitors. When binding studies were conducted on cultured testicular interstitial cellular fractions that are normally discarded during Leydig cell purification, bFGF receptors were identified in these fractions. These results demonstrate that bFGF can have direct effects on Leydig cells through specific receptors; however, because other interstitial cell type(s) also have bFGF receptors, they stress the importance of using highly purified cells when evaluating bFGF actions on Leydig cells.
Mol Cell Endocrinol 1992 Oct
PMID:Evidence for basic fibroblast growth factor receptors in cultured immature Leydig cells. 145 39

Our object was to obtain information about the regulatory mechanism which modulates the effect of basic fibroblast growth factor (bFGF) on commitment to growth in human umbilical vein endothelial (HUVE) cells. Firstly, phorbol ester PMA, a known activator of protein kinase C (PKC), was found to be able to act synergistically with bFGF to stimulate 3H thymidine incorporation in HUVE cells. Secondly, bFGF and PMA induced a stimulated phospholipase A2 (PLA2)-catalyzed release of 14C arachidonate. Thirdly, inhibitors of PLA2, PKC and HETE, but not an inhibitor of cyclooxygenase metabolites, inhibited FGF/PMA-stimulated DNA synthesis. Fourth, the stable cyclooxygenase metabolite of prostacyclin was not found to be changed when cells were treated with bFGF plus PMA. The present data suggest that PKC is able of acting synergistically with bFGF in order to stimulate DNA-primary initiation activity in HUVE cells via the PLA2-dependent generation of lipoxygenase metabolites such as HETE.
Cell Mol Biol 1992 Jul
PMID:Possible involvement of arachidonic acid metabolites in the synergistic action of endothelial mitogenesis by basic fibroblast growth factor and phorbol ester. 149 42

Growth of the normal and malignant prostate is known to be regulated by androgens. Part of their effect has been suggested to be mediated through coordinated regulation of secreted growth factors with autocrine function. We now examine the biological role of preferentially paracrine acting factors in growth control of prostate cancer, i.e. fibroblast growth factor(s) (FGF). Coculture experiments using the androgen-responsive human prostate carcinoma cell line LNCaP as feeder cells and the FGF-dependent human adrenal carcinoma SW-13 cell line as target cells show that (i) LNCaP cells induce growth of SW-13 cells, (ii) even higher stimulation of SW-13 cells is seen in the presence of androgen treated LNCaP cells and (iii) a specific anti-bFGF antibody inhibits growth of SW-13 cells induced by androgen treated LNCaP cells; no proliferation of SW-13 cells occurs in the absence of LNCaP cells. Partial purification of the secretory products of LNCaP cells was performed by affinity chromatography using a heparin sepharose column. Fractions were tested for biological activity in a soft agar assay with SW-13 cells. Several activities could be detected, the main activity was eluted with about 1.5 M NaCl. These data suggest that androgen treatment of LNCaP cells leads to enhanced secretion of proteins which belong to the FGF-family.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Regulation of fibroblast growth factor-like protein(s) in the androgen-responsive human prostate carcinoma cell line LNCaP. 156 38


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