SEARCH · PubMed Health

Results for “FGF”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1977

Effects of fibroblast and epidermal growth factors on ovarian cell proliferation in vitro. I. Characterization of the response of granulosa cells to FGF and EGF.

Despite numerous studies on the effects of gonadotropins on ovarian cells in tissue culture, the factors controlling the proliferation of granulosa cells in vitro remain unknown. We have examined the effect of fibroblast growth factor (FGF) and epidermal growth factor (EGF) on granulosa cell proliferation in vitro in an attempt to clarify their possible roles in the control of ovarian development. FGF and EGF both stimulate DNA synthesis in resting populations of granulosa cells. The half-maximal response forthis effect with FGF was observed at 4 X 10(-11)M and with EGF at 1.5 X 10(-13)M. Autoradiography demonstrated that the whole cell population initiated DNA synthesis in the presence of either EGF or FGF, thus precluding an additive effect of the two mitogens. When cells were maintained at low density (100 cells/cm2) in the presence of low serum (1%) they divided with a doubling time of 48-72 h, but addition of either EGF or FGF accelerated their proliferation. The doubling time observed in the presence of FGF was 16 h versus 20 h with EGF and the final cell density reached in the presence of EGF or FGF was 20 times that of cells maintained in the presence of 1% calf serum alone. In the presence of 10% serum, granulosa cells had a doubling time of 24 h and the final density reached was similar to that observed in 1% serum with EGF and FGF. Addition of EGF or FGF to 10% serum resulted in a final density 3 to 4-fold higher than that observed with 10% serum alone. The ultrastructure of the granulosa cells grown in the presence of EGF or FGF was similar to that of cells maintained in the absence of added mitogens. The only marked difference was that cells grown in the presence of FGF or EGF had a high lipid granule content while cells grown in their absence had a low lipid granule content. The effect of various concentrations of FGF and EGF on the proliferation of granulosa cells has been analyzed. The minimal effective dose of EGF was 3 X 10(-14)M and saturation was observed at 3 X 10(-11)M, with a half-maximal response at 6 X 10(-13)M. With FGF the minimal dose stimulating proliferation was 1.5 X 10(-12)M and saturation was achieved at 1.5 X 10(-10)M, with a half-maximal response at 3 X 10(-11)M. Our results show that EGF and FGF are the most potent mitogens ever observed and are mitogenic for granulosa cells at 300 to 3000-fold lower concentrations than for other cell types which have been studied, such as fibroblasts or lens epithelial cells.

Blood↗

PubMed1977

Effects of fibroblast and epidermal growth factors on ovarian cell proliferation in vitro. II. Proliferative response of luteal cells to FGF but not EGF.

The effect of fibroblast growth factor (FGF) and epidermal growth factor (EGF) on luteal cell proliferation in vitro has been examined. Luteal cells maintained in the presence of low serum (1%) go through a doubling after 7 days. Addition of EGF induced one more doubling of the cells, after which the cells became resting. In contrast, FGF induced the cells to divide logarithmically with a cell cycle of 48 h. The effect of FGF was dependent on the serum and FGF concentrations. It has been obtained with serum concentrations ranging from 0.1% to 10% and with FGF concentrations ranging from 0.1 ng to 10 ng/ml. The half-maximal FGF response was observed at 1.5 x 10(-11)M. In contrast, EGF has no effect besides causing an initial cell doubline within the same range of serum or FGF concentrations. Since granulosa cells have been shown to be highly sensitive to EGF as well as FGF, it can be concluded that during the luteinization process that sensitivity of the cells to EGF is lost, while the sensitivity of FGF is retained. This demonstrates that although luteal cells and granulosa cells are interrelated cell types their sensitivity to growth factors such as EGF is quite different.

Blood↗

PubMed2021

ERBB3 overexpression due to miR-205 inactivation confers sensitivity to FGF, metabolic activation, and liability to ERBB3 targeting in glioblastoma.

In glioblastoma (GBM), the most frequent and lethal brain tumor, therapies suppressing recurrently altered signaling pathways failed to extend survival. However, in patient subsets, specific genetic lesions can confer sensitivity to targeted agents. By exploiting an integrated model based on patient-derived stem-like cells, faithfully recapitulating the original GBMs in vitro and in vivo, here, we identify a human GBM subset (∼9% of all GBMs) characterized by ERBB3 overexpression and nuclear accumulation. ERBB3 overexpression is driven by inheritable promoter methylation or post-transcriptional silencing of the oncosuppressor miR-205 and sustains the malignant phenotype. Overexpressed ERBB3 behaves as a specific signaling platform for fibroblast growth factor receptor (FGFR), driving PI3K/AKT/mTOR pathway hyperactivation, and overall metabolic upregulation. As a result, ERBB3 inhibition by specific antibodies is lethal for GBM stem-like cells and xenotransplants. These findings highlight a subset of patients eligible for ERBB3-targeted therapy.

Antibodies↗

PubMed1978

Control of proliferation of human vascular endothelial cells. Characterization of the response of human umbilical vein endothelial cells to fibroblast growth factor, epidermal growth factor, and thrombin.

Because the response of human endothelial cells to growth factors and conditioning agents has broad implications for our understanding of wound healing angiogenesis, and human atherogenesis, we have investigated the responses of these cells to the fibroblast (FGF) and epidermal growth factors (EGF), as well as to the protease thrombin, which has been previously shown to potentiate the growth response of other cell types of FGF and EGF. Because the vascular endothelial cells that form the inner lining of blood vessels may be expected to be exposed to high thrombin concentrations after trauma or in pathological states associated with thrombosis, they are of particular interest with respect to the physiological role of this protease in potentiating cell proliferation. Our results indicate that human vascular endothelial cells respond poorly to either FGF or thrombin alone. In contrast, when cells are maintained in the presence of thrombin, their proliferative response to FGF is greatly increased even in cultures seeded at a density as low as 3 cells/mm2. Human vascular endothelial cells also respond to EGF and thrombin, although their rate of proliferation is much slower than when maintained with FGF and thrombin. In contrast, bovine vascular endothelial cells derived from vascular territories as diverse as the bovine heart, aortic arch, and umbilical vein respond maximally to FGF alone and neither respond to nor bind EGF. Furthermore, the response of bovine vascular endothelial cells to FGF was not potentiated by thrombin, indicating that the set of factors controlling the proliferation of vascular endothelial cells could be species-dependent. The requirement of cultured human vascular endothelial cells for thrombin could explain why the human cells, in contrast to bovine endothelial cells, are so difficult to maintain in tissue culture. Our results demonstrate that by using FGF and thrombin one can develop cultures of human vascular endothelial cells capable of being passage repeatedly while maintaining a high mitotic index. The stock cultures used for these studies have been passed weekly with a split ratio of 1 to 10 and are currently in their 30th passage. These cultures are indistinguishable from earlier passages when examined for the presence of Weibel-Palade bodies or Factor VIII antigen. We conclude that the use of FGF and thrombin can prevent the precocious senescence observed in most human endothelial cells cultures previously described.

Animals↗

PubMed1979

Vascular endothelial cells maintained in the absence of fibroblast growth factor undergo structural and functional alterations that are incompatible with their in vivo differentiated properties.

Vascular endothelial cells cultured in the presence of fibroblast growth factor (FGF) adopt at confluence a morphological appearance similar to that of the vascular endothelium in vivo. Similarly, their apical cell surface is, as in vivo, nonthrombogenic. In contrast, when the cultures are maintained in the absence of FGF, the cells undergo within two to three passages structural and functional alterations that are incompatible with their in vivo morphological appearance and physiological function. Cultures maintained in the absence of FGF no longer adopt, upon reaching confluence, the configuration of a monolayer composed of small closely apposed and nonoverlapping, cuboidal cells. Instead, confluent cultures deprived of FGF consist of large, overlapping cells which have lost the polarity of cell surface characteristic of the vascular endothelium. The apical cell surface becomes thrombogenic, as reflected by its ability to bind platelets, whereas fibronectin, which at confluence is normally associated only with the basal cell surface, can be found both on top of and underneath the cell layer. Among other changes, both sparse and confluent cultures maintained in the absence of FGF showed a greatly increased production of fibronectin. CSP-60, a cell surface protein whose appearance is correlative with the adoption of a cell monolayer configuration, can no longer be detected in cultures maintained in the absence of FGF. Overlapping endothelial cells maintained in the absence of FGF can also no longer function as a protective barrier against the uptake of ligands such as low density lipoprotein. Exposure of the culture to FGF induces a restoration of the normal endothelial characteristics concomitant with the adoption of a flattened cell monolayer morphology. These results demonstrate that, in addition to being a mitogen. FGF is involved in controlling the differentiation and phenotypic expression of the vascular endothelium. This is reflected by its effect on the morphological appearance, polarity of cell surfaces, platelet binding capacity, and barrier function of the vascular endothelium.

Animals↗

PubMed1977

Control of bovine adrenal cortical cell proliferation by fibroblast growth factor. Lack of effect of epidermal growth factor.

Primary functional bovine adrenal cortical cell cultures have been developed to study the factors controlling adrenal cell growth. Cells were prepared by the collagenase technique and maintained in F-12 medium containing fetal calf serum and horse serum. Cells contained abundant lipid as demonstrated by staining with Oil Red O and showed strongly positive staining for delta5,3beta-hydroxysteroid dehydrogenase. ACTH inhibited DNA synthesis and stimulated steriodogenesis in these cells. Fibroblast growth factor (FGF) was shown to be a potent stimulator of the growth of normal bovine adrenal cortical cells maintained in tissue culture. The minimal effective dose of FGF was 1 ng/ml with maximal effects being observed at 100 ng/ml. The effect of FGF was dependent on the serum concentration. Inclusion of FGF in F-12 medium containing serum permitted cloning of functional bovine adrenal cortical cells from cultures seeded at low density (4 cells/cm2). ACTH inhibited the mitogenic effects of FGF. In addition to its mitogenic action, FGF is a migratory factor for bovine adrenal cortical cells. Though ACTH inhibited the mitogenic effects of FGF, it did not block the migratory activity. Epidermal growth factor did not affect the growth of either normal bovine adrenal or functional mouse adrenal tumor cells (Y-1) in tissue culture. FGF is the first direct mitogen identified for adrenal cortical cells; ACTH opposes this mitogenic action and functions directly as a differentiate function signal.

Adrenal Cortex↗

PubMed1978

Purification of the fibroblast growth factor activity from bovine brain.

The purification of the fibroblast growth factor (FGF) from bovine brain has led to the isolation of two peptides. FGF-1 with 128 amino acids and FGF-2 with 107 amino acids. The biological activity of these two peptides is acid- and heat-labile. As indicated by the amino acid composition of FGF-1 and -2, these two peptides are derived from a common precursor and bear no resemblance to pituitary FGF. The brain FGF peptides, like pituitary FGF, are mitogenic in vitro for the same wide variety of mesoderm-derived cells. Since their mitogenic activity is acid- and heat-labile, they are thereby distinguished from the platelet factor isolated from platelets and from the cationic peptide isolated from serum which has been shown to have the same molecular weight and isoelectric point as brain and pituitary FGF.

Amino Acids↗

PubMed1977

Control of proliferation of bovine vascular endothelial cells.

The effects of Fibroblast Growth Factor (FGF) and Epidermal Growth Factor (EGF) on the proliferation of bovine vascular endothelial cells has been examined. FGF induces the initiation of DNA synthesis and cell proliferation in cloned endothelial cells of fetal and adult origin at concentrations as low as 1 ng/ml and is saturating at 50 ng/ml. EGF had no effect over the same range of concentrations. The mitogenic effect of FGF is blocked by a crude extract of cartilage. Platelet extract is also mitogenic for vascular endothelial cells although to a lesser extent than the purified FGF. In contrast to vascular endothelial cells, both EGF and FGF are mitogenic for vascular smooth muscle cells although EGF is less mitogenic than FGF at 100 ng/ml. The mitogenic effect of EGF and FGF on vascular smooth muscle is not blocked by the addition of a crude extract of cartilage, thus demonstrating the specificity of the chalone like effect of cartilage crude extract for endothelial cells.

Animals↗

PubMed1978

Brain-derived fibroblast growth factor: identity with a fragment of the basic protein of myelin.

Fibroblast growth factors (FGF) isolated from bovine brain have been identified chemically and immunologically as components of the myelin basic protein. The intact bovine basic protein molecule (170 residues), prepared by the standard acid extraction procedure, lacked mitogenic activity (tested at concentrations up to 10 microgram/ml). However, the polypeptide FGF-2, identified as residues 44-153 of the basic protein, was maximally mitogenic for fibroblasts at 10 ng/ml and polypeptide 44-166 (FGF-1) was maximally active at 100 ng/ml. Pituitary-derived FGF is a potent a growth factor as FGF-2, but appears to be biochemically and immunologically distinct from brain-derived FGF. FGF released in the central or peripheral nervous system as a consequence of myelin damage and basic protein proteolysis could provide a physiological stimulus for wound healing and myelin repair.

Amino Acid Sequence↗

PubMed1979

Fibroblast and epidermal growth factors are mitogenic agents for cultured granulosa cells of rodent, porcine, and human origin.

The mitogenic effects of epidermal growth factor (EGF) and fibroblast growth factor (FGF) on cultured granulosa cells of different species have been analyzed. EGF and FGF are potent mitogenic agents for rabbit, porcine, and human granulosa cell cultures. While guinea pig granulosa cell cultures respond to FGF, they were hardly effected by EGF. Rat granulosa cell cultures did not respond markedly to either EGF or FGF. Our results, therefore, demonstrate that the mitogenic effects of EGF and FGF are not restricted to granulosa cells of bovine origin and, with the exception of rat granulosa cells, cultured granulosa cells responded either to FGF alone or to both EGF and FGF with a marked increase in their rates of proliferation.

Animals↗

PubMed1975

Stimulation of division of Y1 adrenal cells by a growth factor isolated from bovine pituitary glands.

The effect of Fibroblast Growth Factor (FGF) on the initiation of DNA synthesis and on the rate of division of the Y1 adrenal cell line has been investigated. In sparse populations of Y1 cells (4 times 10- minus 3 cells/cm2) maintained in 0.2 percent calf serum, FGF was able to initiate DNA synthesis to the same extent that an optimal concentration of serum could. Cells maintained in 0.2 percent calf serum sustained continuous growth when given 5 ng/ml of FGF daily. Cultures fixed and stained with crystal violet showed FGF colonies to be of equivalent size and quantity as those with serum alone. Insulin had no mitogenic activity of its own at concentrations as high as 500 ng/ml nor did it have any potentiating effect on the mitogenic activity of FGF. Glucocorticoids (0.1 mug/ml to 1 mug/ml) inhibited (25 percent) the initiation of DNA synthesis as well as the rate of division induced by FGF. ACTH (0.75 IU/ml) was clearly inhibitory. Not only did it reduce the rate of division of cells in serum but it also reduced the rate of DNA synthesis and inhibited division in the presence of FGF.

Adrenal Gland Neoplasms↗

PubMed1977

The regulation by fibroblast growth factor of early transport changes in quiescent 3T3 cells.

This study involves the use of fibroblast growth factor (FGF) as a substitute for exogenous serum to examine the early transport changes which occur when quiescent 3T3 cells re-initiate active growth. FGF, in nanogram amounts, together with insulin and dexamethasone, can induce mitogenesis and mitosis in 3T3 cells GO-arrested by holding in growth medium containing 0.8% calf serum. In terms of quiescent cell transport activity enhancement, FGF is 300,000-fold more effective than fresh serum, on a protein basis. In addition, very short exposure of serum-depleted cells to FGF indicates that a distinct temporal or time sequence exists in the transport system activation process. For example, uptake of alpha-aminoisobutyric acid (AIB) and uridine are stimulated very rapidly, whereas hypoxanthine uptake does not respond until much later. Closer analysis shows that AIB uptake is maximally enhanced within zero to two minutes after FGF addition to cells. Finally, the stimulatory effect of FGF on transport system activities is specific in terms of the proliferative state of the cells to which it is added, and in terms of the uptake systems which respond to it.

Adenosine↗

PubMed1976

Effect of fibroblast growth factor on the division and fusion of bovine myoblasts.

The effect of fibroblast growth factor (FGF) on the rate of proliferation and fusion of bovine myoblast has been examined. Addition to the cultures of 0.1 mug-1 mug/ml of FGF stimulates the rate of proliferation and delays the fusion of primary cultures of bovine myoblasts cultured in 10% serum. Final cell densities reached in the presence of 0.1 mug/ml of FGF were fivefold higher than in controls; with 1 mug/ml, they were 10-fold higher. Increases in cell density were paralleled by increases in acetylcholine receptor sites as measured by the binding of 125I-alpha-bungarotoxin. Both fusion and the appearance of acetylcholine receptor sites were delayed in the presence of FGF. Growth hormone, insulin and testosterone, which have been reported to be mitogenic for rat and chick embryo myoblasts, did not have significant effects on DNA synthesis in bovine myoblasts when compared to the FGF. Conversely, FGF did not stimulate the proliferation of chick embryo myoblasts, indicating that it is not active in all vertebrate species.

Acetylcholine↗

PubMed1975

Pituitary fibroblast growth factor as a stimulator of growth in cultured rabbit articular chondrocytes.

Growth promoting activity for rabbit chondrocytes has been described as a contaminant of partially pruified TSH and LH prepared from bovine and ovine pituitaries. We have investigated fibroblast frowth factor (FGF), a small growth promoting peptide isolated from bovine pituitary tissue, in a rabbit chondrocyte system. The results suggest to us that FGF is the factor or one of the factors responsible for chondrocyte growth stimulating activity previously described in the pituitary hormone preparations. DNA synthesis in these cells is stimulated by FGF at final medium concentrations of 10(-9) g/ml. Bovine NIH-LH is not stimulatory below concentrations of 10(-7) g/ml. FGF also stimulates cell growth in the presence of 10% fetal bovine serum. Dexamethasone, at concentrations of 10(-5) to 10(-9) g/ml exerts a synergistic effect with FGF on both DNA synthesis and cell growth. Over a concentration range of 10(-6) to 10(-9) g/ml, FGF does not stimulate synthesis of sulfated mucopolysaccharides.

Animals↗

PubMed1977

A comparison of the responses of cultured myoblasts and chondrocytes to fibroblast and epidermal growth factors.

The effects of fibroblast and epidermal growth factors on proliferation and differentiation of cultured myoblasts and chondrocytes have been compared. FGF stimulated myoblast proliferation, as determined by monitoring levels of DNA synthesis during seven days growth in vitro and by the morphology of the cultures after myotube formation. EGF has relatively little effect on myoblast proliferation. With chondrocytes, both FGF and EGF are mitogenic and FGF's, but not EGF's effect is potentiated by dexamethasone. One implication of these results is that in the course of differentiation cell types which develop from the same embryonic origin as fibroblasts are controlled by different sets of mitogenic factors. Myoblasts become primarily dependent on mitogenic agents such as FGF while chondrocytes can respond to both FGF and EGF.

Cartilage↗

PubMed1979

Structural and functional alterations in the surface of vascular endothelial cells associated with the formation of a confluent cell monolayer and with the withdrawal of fibroblast growth factor.

Vascular endothelial cells cultured in the presence of fibroblast growth factor (FGF) divide actively when seeded at low or clonal cell densities and upon reaching confluence adopt a morphologic appearance and differentiated properties similar to those of the vascular endothelium in vivo. In this review, we present some of our recent observations regarding the characteristics (both structural and functional) of these endothelial cells and the role of FGF in controlling their proliferation and normal differentiation. At confluence the endothelial cells form a monolayer of closely apposed and nondividing cells that have a nonthrombogenic apical surface and can no longer internalize bound ligands such as low-density lipoprotein (LDL). The adoption of these properties is correlated and possibly causally related to changes in the cell surface such as the appearance of a 60,000 molecular weight protein (CSP-60); the disappearance of fibronectin from the apical cell surface and its concomitant accumulation in the basal lamina; and a restriction of the lateral mobility of various cell surface receptor sites. In contrast, endothelial cells that are maintained in the absence of FGF undergo within three passages alterations that are incompatible with their in vivo morphologic appearance and physiologic behavior. They grow at confluence on top of each other and hence can no longer adopt both the structural (CSP-60, cell surface polarity) and functional (barrier function, nonthrombogenicity) attributes of differentiated endothelial cells. Since these characteristics can be reacquired in response to readdition of FGF, in addition to being a mitogen FGF may also be involved in controlling the differentiation and phenotypic expression of the vascular endothelium.

Animals↗

PubMed1979

An endothelial cell growth factor from bovine hypothalamus: identification and partial characterization.

Extracts of bovine hypothalamus were found to contain a significant level of mitogenic activity when tested in a Swiss 3T3 cell [3H]dThd incorporation assay and in a human umbilical vein endothelial cell growth assay. The mitogenic activity responsible for 3T3 cell activity was purified and characterized as a fibroblast growth factor (FGF)-like mitogen. Neither the biologically active FGF-like mitogen purified from the hypothalamus extracts nor FGF purified from bovine pituitary glands was mitogenic when added to human endothelial cells in vitro, suggesting the presence of more than one mitogen in the hypothalamic extracts. The 3T3 and endothelial cell biological activities of hypothalamic extracts were both found to be inactivated by trypsin, subtilisin, and heat treatment, but were stable to dialysis. The endothelial cell growth factor activity could be efficiently separated from the FGF activity by gel exclusion chromatography. The endothelial cell mitogen possessed a molecular weight of approximately 75,000, whereas that of FGF was approximately 15,000. The endothelial cell growth factor activity was found to be inactivated with reducing agents whereas the 3T3 cell mitogenic activity was stable after incubation with 2-mercaptoethanol. Significant levels of endothelial cell mitogenic activity were also found in extracts of bovine brain and pituitary glands.

Animals↗

PubMed1976

Studies of human diploid fibroblast growth. I. Responses of normal and hypopituitary cells to fibroblast growth factor, insulin, and serum.

We have assayed the growth stimulating activity of bovine insulin, fibroblast growth factor (FGF), and fetal bovine serum (FBS) in diploid human fibroblasts from normal and idiopathic hypopituitary donors. All three factors stimulated DNA synthesis in cells arrested by serum starvation. FGF was active at concentrations as low as 5 ng/ml with maximum effect at 100 ng/ml. FGF stimualted DNA synthesis at lower concentrations than did insulin and also produced a greater maximum response. Only serum was capable of supporting cell division and growth, but FGF accellerated this growth rate when it was added to serum-containing medium. Hydrocortisone, actinomycin D, and cycloheximide inhibit FGF stimulation. There was no significant difference between fibroblasts from normal and hypopituitary donors.

Animals↗