Biomedical subjects

Y Courtois

Publications and source records attributed to Y Courtois.

At least 55 records · Page 3Linked to original sources

PubMed1998

Paracrine effects of phosphorylated and excreted FGF1 by retinal pigmented epithelial cells.

We have recently shown that both inhibition of endogenous Fibroblast growth factor (FGF) synthesis in non dividing lens epithelial cells (Renaud et al. J. Biol. Chem 1996, 271: 2801-2811) and inhibition of secreted FGF1 in confluent quiescent retinal pigmented epithelial (RPE) cells (Guillonneau et al., Exp. Cell. Res. 1997, in press) induce rapid cell apoptosis. In addition, FGF2-stimulated release of endogenous FGF1 is associated with reduced apoptosis in RPE cells. We now show that a single addition of exogenous FGF2 to RPE cells induces after 4 days of culture, a great accumulation of FGF1 within the cells. Concomitantly we observe that FGF1 was released into the extracellular medium. Secreted FGF1 from RPE cells, purified from culture medium and added to either Go-arrested RPE or RMG cells at low plating density induced cell proliferation, whereas when it is added once to serum-depleted confluent RPE and RMG cells it prevented apoptosis. Both endogenous and secreted FGF1 are phosphorylated. In addition, FGF2 stimulated the production and release of phosphorylated FGF1 by RPE cells. We show that this secreted form of phosphorylated FGF1 binds to the high affinity tyrosine kinase receptors of RPE and RMG cells on retinal sections and to heparan sulfate proteoglycan in RPE cell extracellular matrix. In contrast to non-phosphorylated FGF1, phosphorylated secreted FGF1 was not degraded after internalization but accumulated within RPE and RMG cells, and is rapidly translocated to the nucleus suggesting a role in signal transduction and gene expression pathways. These results show that exogenous FGF2 activities might be mediated indirectly by phosphorylation and that secretion of FGF1 may function as a paracrine trophic factor for retinal cells.

Animals↗

PubMed1998

Reduction of corneal edema in endotoxin-induced uveitis after application of L-NAME as nitric oxide synthase inhibitor in rats by iontophoresis.

PURPOSE: To investigate the involvement of the cornea during endotoxin-induced uveitis (EIU) in the rat and the effect of Ngamma-nitro-L-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor, administered by iontophoresis. METHODS: EIU was induced in Lewis rats that were killed at 8 and 16 hours after lipopolysaccharide (LPS) injection. The severity of uveitis was evaluated clinically at 16 hours, and nitrite levels were evaluated in the aqueous humor at 8 hours. Corneal thickness was measured, 16 hours after LPS injection, on histologic sections using an image analyzer. Transmission electron microscopy (TEM) was used for fine analysis of the cornea. Transcorneoscleral iontophoresis of L-NAME (100 mM) was performed either at LPS injection or at 1 and 2 hours after LPS injection. RESULTS: At 16 hours after LPS injection, mean corneal thickness was 153.7+/-5.58 microm in the group of rats injected with LPS (n=8) compared with 126.89+/-11.11 microm in the saline-injected rats (n=8) (P < 0.01). TEM showed stromal edema and signs of damage in the endothelial and epithelial layers. In the group of rats treated by three successive iontophoreses of L-NAME (n=8), corneal thickness was 125.24+/-10.36 microm compared with 146.76+/-7.52 microm in the group of rats treated with iontophoresis of saline (n=8), (P=0.015). TEM observation showed a reduction of stromal edema and a normal endothelium. Nitrite levels in the aqueous humor were significantly reduced at 8 hours by L-NAME treatment (P=0.03). No effect on corneal edema was observed after a single iontophoresis of L-NAME at LPS injection (P=0.19). Iontophoresis of saline by itself induced no change in corneal thickness nor in TEM structure analysis compared with normal rats. CONCLUSIONS: Corneal edema is observed during EIU. This edema is significantly reduced by three successive iontophoreses of L-NAME, which partially inhibited the inflammation. A role of nitric oxide in the corneal endothelium functions may explain the antiedematous effect of L-NAME.

Animals↗

PubMed1997

Inhibition of inducible nitric oxide synthase expression by interferons alpha and beta in bovine retinal pigmented epithelial cells.

Bovine retinal pigmented epithelial (RPE) cells express an inducible nitric oxide synthase (NOS-2) after activation with interferon (IFN)-gamma and lipopolysaccharide (LPS). Experiments were performed to investigate the effects of IFN-alpha and IFN-beta on NOS-2 activity. These types of interferons did not aid LPS in the production of nitrite, but markedly inhibited in a concentration-dependent manner the nitrite release due to LPS/IFN-gamma. Analysis by Western and Northern blots showed that RPE cells co-stimulated with IFN-alpha or IFN-beta with LPS/IFN-gamma accumulated lower levels of NOS-2 protein and mRNA than in the presence of LPS/IFN-gamma alone. The presence of IFN-alpha or IFN-beta did not accelerate mRNA degradation, implying that these interferons did not affect NOS-2 mRNA stability, but more probably NOS-2 gene expression. Furthermore, IFN-gamma binding studies demonstrated that the inhibitory effect of IFN-alpha and IFN-beta is not caused by a blocking of IFN-gamma receptors. Analysis of NF-kappaB activation by electrophoretic mobility shift assay demonstrated that LPS/IFN-gamma-induced NF-kappaB binding was not changed by the presence of IFN-alpha. However, similar experiments revealed that the activation of interferon regulatory factor-1 (IRF-1) by LPS/IFN-gamma was decreased by IFN-alpha. This phenomenon could be due to the decline of IRF-1 mRNA and the up-regulation of IRF-2 mRNA, an IRF-1 repressor, by IFN-alpha. These results suggest that the inhibitory effect of IFN-alpha and -beta on NOS-2 induction could be partially explained by their effect on the induction of the IRFs, which were involved in NOS-2 gene transcription.

Animals↗

PubMed1997

Control of nitric oxide production by endogenous TNF-alpha in mouse retinal pigmented epithelial and Muller glial cells.

Since the induction of nitric oxide synthase (NOS) by lipopolysaccharide (LPS) has been suggested to be partially dependent of the synthesis of tumor necrosis factor alpha (TNF alpha), we have investigated in vitro the production of NO in retinal cells from mice deficient in Lymphotoxin alpha (LT alpha)/TNF alpha. Treatment of retinal Müller glial (RMG) and retinal pigmented epithelial (RPE) cells from both wild-type and knockout mice with LPS and interferon gamma (IFN gamma) induced NO synthesis as determined by nitrite release into the media and was correlated to an increase in NOS-2 mRNA levels, evaluated by RT-PCR. However, the level of nitrite and the accumulation of mRNA was always less in cells from LT alpha/TNF alpha knockout mice than in wild type mice. Simultaneous addition of TNF alpha restored the level of NO synthesis by RMG and RPE cells from LT alpha/TNF alpha knockout mice stimulated with LPS and IFN gamma to wild type levels. Transforming growth factor beta (TGF beta) blocked LPS/IFN gamma-induced NO production is RMG and RPE cells from wild-type and LT alpha/TNF alpha knockout mice. Our results demonstrate that induction of NO synthesis in RMG and RPE cells by LPS and IFN gamma is dependent in part on endogenous TNF alpha while inhibition of NO production by TGF beta does not require a modulation of TNF alpha synthesis.

Animals↗

PubMed1997

Comparative study in vivo and in vitro of uniformly 14C-labelled and 125I-labelled recombinant fibroblast growth factor 2.

Recombinant bovine fibroblast growth factor (FGF2), uniformly labelled with 14C ([14C]FGF2), was purified and showed to be highly stable and to retain full biological activity. Organ distribution of [14C]FGF2 after intravenous injection of young rats was assessed by autoradiography of whole body sections and compared with those obtained with [125I]iodinated FGF2 (125I-FGF2). Thyroid, stomach, intestine, bladder and skin were radioactively labelled only in the case of 125I-FGF2. This tissue-labelling is artefactual, probably due to free iodide binding not observed when using [14C]FGF2. High-resolution autoradiography showed a complex tissue distribution of [14C]FGF2 in kidney and adrenal organs. Incubation of frozen eye sections with [14C]FGF2 showed a specific and high-resolution labelling pattern of ocular tissues. After cellular internalization, [14C]FGF2 was processed into five distinct polypeptides of 16, 14, 8, 7, and 5.5 kDa. The 14-kDa and 7-kDa polypeptides are novel catabolic fragments not detected with radioiodinated FGF2. In terms of stability, tissue distribution specificity, and autoradiographic resolution, [14C]FGF2 proved to have more advantages than 125I-FGF2 for pharmacokinetic and catabolism studies.

Adrenal Glands↗

PubMed1997

Developmental expression of nitric oxide synthase isoform I and III in chick retina.

During our studies on the multiple possible functions of nitric oxide (NO) in chick retinal development and physiology, we have demonstrated the presence and the activity of NO synthase (NOS-I and III) in certain neuronal populations (photoreceptors, amacrine cells in the inner nuclear and ganglion cells) and also in synaptic-rich regions in the developing chick retina. Both enzymes, detected by nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase, immunohistochemistry and Western blotting, appeared between embryonic days 6 and 12, and followed a spatial and temporal pattern of expression which correlated with the differentiation of the neuronal layers. Evaluation of the conversion of [3H]-labeled arginine to [3H]-citrulline, confirmed the presence of a calcium-dependent NOS activity in the cytosolic and particulate retinal extracts during the development. This pattern of NOS expression suggests that the regulated release of NO during key phases of development might be one mechanism involved in the regulation of retinal differentiation.

Animals↗

PubMed1997

FGF2-stimulated release of endogenous FGF1 is associated with reduced apoptosis in retinal pigmented epithelial cells.

Both inhibition of endogenous fibroblast growth factor (FGF) synthesis on nondividing lens epithelial cells and inhibition of secreted FGF1 in confluent quiescent retinal pigmented epithelial (RPE) cells induce rapid cell apoptosis (Renaud et al., 1996, J. Biol. Chem., 271, 2801-2811). In addition several studies demonstrate that exogenous FGF2 can promote retinal cell survival in vitro and in vivo. To determine the possible relationship between exogenous FGF2, endogenous FGF1, and cell survival, we examined the protective effect of a single dose of exogenous FGF2 on long-term culture of quiescent RPE cells after serum withdrawal. After 4 days of culture, a dramatic and sustained upregulation of FGF1 protein expression occurs specifically in response to exogenous FGF2. After addition of FGF2 (20 ng/ml), RPE cells express fourfold more FGF1 after Day 7 than after Day 1 of culture. This phenomenon is FGF2 dose-dependent. In contrast, neither serum nor FGF2 have an effect on total endogenous FGF2 expression. In addition, in response to exogenous FGF2, FGF1 is secreted in significant amounts into the extracellular medium at a rate comparable to FGF1 accumulation within the cell. Furthermore, in the absence of serum, significant increase in cell death occurs on Day 6 of culture, whereas addition of exogenous FGF2 induces a twofold decrease of RPE cell apoptosis. In the presence of exogenous FGF2, addition of a specific anti-FGF1 neutralizing antibody induces a rapid apoptosis of RPE cell cultures. Thus, we speculate that exogenous FGF2 may indirectly prolong cell survival by increasing synthesis and secretion of endogenous FGF1 and that endogenous FGF1, directly in response to exogenous FGF2, may function as an autocrine trophic factor in RPE cells.

Animals↗

PubMed1997

Fibroblast growth factor receptors and regeneration of the eye lens.

If the eye lens of the adult newt, Notophthalmus viridescens, is removed, a new lens will regenerate and only from the dorsal, not the ventral, iris. The source, pigmented epithelial cells, would normally no longer divide, but upon lentectomy they do re-enter the cell cycle and form lens. The cause for this capability is unknown, but the mitogenic Fibroblast Growth Factors and their receptors may be involved. We have demonstrated that FGF receptors are present and operative in lens regeneration, since receptor-directed mitotoxins inhibit regeneration; heterogeneity and differential density in FGF-binding and receptor localization in iris sectors is also present. We propose that the spatial distribution of FGF receptors, especially the amphibian homolog of FGFR-3, is important in initiation of regeneration of eye lens.

Animals↗

PubMed1997

Iontophoresis of dexamethasone in the treatment of endotoxin-induced-uveitis in rats.

The purpose of this study was to evaluate the efficacy of a Coulomb Controlled Iontophoresis system (CCI) in the local delivery of corticosteroids for the treatment of uveitis. The therapeutic efficacy of Dexamethasone (Dex) administered by CCI was compared to systemic injection and to topical application with the iontophoresis apparatus in the absence of electrical current. The evaluation was done in the treatment of the endotoxin-induced uveitis (EIU) model, and in the effect on TNF gene expression in the iris/ciliary body as well as in the retina and on TNF levels in aqueous humor and vitreous. Dex was administered either at the time of LPS injection or 5 hours later. For iontophoresis, we used a 1 ml reservoir-electrode covering the cornea, the limbus, and the first millimeter of the sclera. The applied electrical current was of 400 microA during four minutes with a total surface charge of 0.4 C cm-2. EIU was evaluated by clinical examination, by counts of intraocular inflammatory cells on histological sections, and by measuring the protein levels in the aqueous humor and in the vitreous. The TNF-alpha gene expression in the iris and ciliary body, and in the retina was evaluated by RT-PCR. The systemic effect of Dex delivered by CCI was evaluated on the level of serum TNF-alpha in EIU. Our results demonstrated that local administration of Dex by CCI inhibited anterior and posterior signs of intraocular inflammation as effectively as systemic administration, with no effect on systemic level of TNF. In the anterior and posterior segments of the eye, the protein exudation. TNF levels and the cellular infiltration were inhibited. The TNF-alpha gene expression was inhibited in the anterior as well as the posterior segment of the eye. No clinical nor histological damage were caused by the CCI apparatus. In conclusion, CCI administration of Dex allows for a therapeutic effect on the posterior as well as the anterior segment of the eye, and may present a viable alternative to systemic administration of glucocorticoids in severe ocular inflammations.

Animals↗

PubMed1997

Fibroblast growth factor 2, heparin and suramin reduce epithelial ulcer development in experimental HSV-1 keratitis.

BACKGROUND: We have previously shown that basic fibroblast growth factor (FGF-2) enhances corneal epithelial healing in different experimental models in vivo. In order to study the healing effect of this growth factor in pathological conditions of the cornea, we investigated whether topical application of FGF-2 could affect herpes keratitis in rabbits. Since HSV-1 infection is prevented in vitro by incubation with heparin, we also topically applied heparin and suramin, considering the similar interaction of herpes simplex virus and FGF-2 with cell membrane-anchored heparan sulfate. METHODS: After virus inoculation with a human BEY.2 strain, rabbits were treated with either FGF-2 (200 ng to 2 micrograms/application), heparin (250 micrograms/application) or suramin (250 micrograms/application) 4 times daily until day 14. Acyclovir and placebo administrations served as controls (n = 48 rabbits). Computerized ulcer surface analysis, clinical observations and virus recovery assays were performed. RESULTS: Topical FGF-2, heparin and suramin treatment revealed a significant reduction in peak ulcer sizes, and complete epithelial healing was achieved earlier than in placebo-treated corneas. However, no significant antiviral effect of FGF-2, heparin and suramin was detectable in plaque assays from conjunctival swabs. CONCLUSIONS: These experiments demonstrate that FGF-2 is effective in promoting herpetic epithelial ulcer healing, either due to its proliferative effects on epithelial cells or indirectly by occupying the sites on cell surface heparan sulfate necessary for the attachment of the virion. The latter mechanism of action is presumably the reason for the similar effect of heparin and suramin.

Acyclovir↗

PubMed1997

On the use of Zn2+ to discriminate endonucleases activated during apoptosis.

One approach to discriminate among specific DNases in apoptosis is to use inhibitors specific for each endonuclease. Zn2+ is known to inhibit Ca(2+)- and Mg(2+)-dependent endonuclease enzymatic activities during apoptosis. Acidic DNases were thought to be insensitive to Zn2+. In this paper, we analyse the effects of Zn2+ on activity of DNase II, either purified or in nuclei from lens fiber cells. These cells follow a physiological nuclear degeneration with DNase II accumulation in their nuclei. We show that Zn2+ is able to inhibit also this acidic endonuclease at a concentration of 1-6 mM. At a higher concentration of Zn2+, DNA is extensively degraded during the assay, masking the inhibition of the enzyme. This DNA degradation in the presence of Zn2+ has led to an overestimation of the activity of DNase II in studies of apoptosis. Hence, Zn2+ cannot be used to specifically identify one endonuclease among the different DNases involved in nuclear degradation during programmed cell death.

Animals↗

PubMed1997

Protection against light-induced retinal degeneration with naftidrofuryl (Praxilene) in the rat.

The purpose of this work was to investigate the ability of Naftidrofuryl (Praxilene, Lipha-Santé, France) to produce light-induced retinal degeneration in the rat. Fisher male rats were injected intraperitoneally with 30 mg/kg Naftidrofuryl in 0.9% NaCl. The first injection took place 30 minutes before the beginning of the constant light exposure (90 fc) and was repeated at days 2 and 4. The animals were sacrificed at day 7. Controls treated or not with Naftidrofuryl were exposed to a regular cyclic light environment (20 fc). Eyes were fixed in 4% paraformaldehyde and embedded in Historesin. Whole median 5 microns sections of the retina were analyzed by measurement of the thickness of the retinal photoreceptor nuclear and inner and outer segment layers with a Biocom image analyzer. After one week of constant illumination, the photoreceptor nuclear layer thickness decreased in all regions of the retina, more in the superior than in the inferior region. In animals treated with Naftidrofuryl, a significant rescue from degeneration was observed throughout all retinal regions. An average rescue of 66% (compared with the retina from constantly illuminated rats) was observed. Naftidrofuryl had no effect on cyclic light-raised rats. Naftidrofuryl partially protects against the degeneration of photoreceptors induced by constant light illumination of the rat retina.

Animals↗

PubMed1997

Expression of inducible nitric oxide synthase in bovine corneal endothelial cells and keratocytes in vitro after lipopolysaccharide and cytokines stimulation.

PURPOSE: To determine whether bovine corneal endothelial (BCE) cells and keratocytes express the inducible form of nitric oxide synthase (NOS) after exposure to cytokines and lipopolysaccharide (LPS), and to study the regulation of NOS by growth factors. METHODS: Cultures of bovine corneal endothelial cells and keratocytes were exposed to increasing concentrations of LPS, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). At selected intervals after exposure, nitrite levels in the supernatants were evaluated by the Griess reaction. Total RNA was extracted from the cell cultures, and messenger RNA levels for inducible NOS (NOS-2) were measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Exposure of BCE cells and keratocytes to LPS and IFN-gamma resulted in an increase of nitrite levels that was potentiate by the addition of TNF-alpha. Analysis by RT-PCR demonstrated that nitrite release was correlated to the expression of NOS-2 messenger RNA in BCE cells and keratocytes. Stereoselective inhibitors of NOS and cycloheximide inhibited LPS-IFN-gamma-induced nitrite release in both cells, whereas transforming growth factor-beta (TGF-beta) slightly potentiated it. Fibroblast growth factor-2 (FGF-2) inhibited LPS-IFN-gamma-induced nitrite release and NOS-2 messenger RNA accumulation in keratocytes but not in BCE cells. CONCLUSIONS: The results demonstrate that in vitro activation of keratocytes and BCE cells by LPS and cytokines induces NOS-2 expression and release of large amounts of NO. The high amounts of NO could be involved in inflammatory corneal diseases in vivo.

Animals↗

PubMed1996

Peroxynitrite cytotoxicity on bovine retinal pigmented epithelial cells in culture.

Peroxynitrite induced in vitro a dose dependent toxicity on retinal pigmented epithelial (RPE) cells. Cell death was partially mediated by apoptosis as demonstrated by nuclear fragmentation and TdT-mediated dUTP nick-end labeling assay. Peroxynitrite-induced tyrosine nitration was revealed by immunocytochemistry, both in the cytoplasm and in the nucleus of the cells. Nitration was not observed in RPE cells, producing nitric oxide (NO) after stimulation by lipopolysacharide and interferon-g (IFN-gamma), suggesting that peroxynitrite was not formed in vitro in such conditions. Peroxynitrite could be responsible for the retinal damages observed in pathological conditions in which NO has been demonstrated to be involved. In this context, EGb761, identified as a free radical scavenger, was showed herein to protect RPE cells against peroxynitrite injury.

Animals↗

PubMed1996

Long term light-induced retinal degeneration in the miniature pig.

In developing a model of slow light-induced retinal degeneration, ten miniature pigs were submitted to constant lighting for a period ranging from one to three months. Post-lighting survival time ranged from zero to two months. Control and illuminated animals were examined for pupillary reflex, underwent fundus examination and an electroretinogram. After euthanasia, retinas were processed for histology with measure of outer nuclear layer thickness. All animals illuminated one or more months had pupillar reflex alteration. Mean outer nuclear thickness was 24.12 microns in the control and ranged from 18.36 to 21.45 microns in illuminated animals (mean reduction 20%). Despite the pigmentation of miniature pigs, consistent results were obtained in the absence of pharmacologic pupil dilation.

Animals↗

PubMed1996

Accumulation of NO synthase (type-I) at the neuromuscular junctions in adult mice.

Recent data have shown that NOS-I is localized almost exclusively to the sarcolemma of fast-twitch fibers, where it probably interacts with the dystrophin-glycoprotein complex. The concentration of dystrophin-related protein at the neuromuscular junctions and the possible involvement of NO in synaptic suppression led us to investigate the presence of NOS-I at the adult motor endplates. Our data clearly show that NOS-I protein, detected by immunohistochemistry accumulates at the adult endplates. Furthermore, the absence of NOS-I protein at the denervated neuromuscular junctions suggest a neural origin of this enzyme. The putative roles of NO at the endplate are discussed.

Animals↗

PubMed1996

Expression of the chicken cysteine-rich fibroblast growth factor receptor (CFR) during embryogenesis and retina development.

The expression of the chicken cysteine-rich fibroblast growth factor receptor (CFR) during organogenesis and specifically during retina formation was studied by Northern blotting and a sensitive in situ hybridization. At days 2 and 4 of embryonic development (E2 and E4), CFR mRNA was present in a wide variety of developing organs; it was abundantly expressed in nervous structures, particularly in the retina. The levels of CFR transcripts were high during the proliferation and the subsequent differentiation phases of retinal neurogenesis, reached a maximum around E11 during the onset of the major period of retinal cell death, and then declined progressively. CFR mRNA was not detected at late stages when the final arrangement of retinal cell layers has been established. In prolonged primary cell cultures of chicken embryo retina, CFR expression showed a similar down-regulation to that seen with increasing age in vivo. It was up-regulated either directly or indirectly by its ligands. The CFR expression pattern in the developing retina was complementary to that of two other fibroblast growth factor (FGF) receptors, namely FGF-R1 and FGF-R2. In regard to a progressive increase in the expression of their ligands during retinal development, we suggest that CFR may have a role distinct from that of the tyrosine kinase FGF receptors during retinogenesis. Finally, the comparison of CFR expression with those of the other high affinity receptors indicates a regulation of the FGF function at the receptor level during neural retina development.

Aging↗

PubMed1996

Expression and regulation by serum of multiple FGF1 mRNA in normal transformed, and malignant human mammary epithelial cells.

In normal (NMEC), transformed (HBL-100) and malignant human mammary epithelial cells (MCF 7, BT-20, MDA-MB 231), we have examined the expression and the regulation by serum of FGF1 and FGF2 mRNA. FGF2 mRNA level was higher in NMEC and in a HBL-100 than in malignant cell lines (MDA-MB-231, BT-20). No FGF2 mRNA was detected in the malignant cell line, MCF-7. In contrast, the FGF1 mRNA was detected in all the mammary epithelial cells but at different levels. NMEC, HBL-100 and MDA-MB231 cells expressed similar level of FGF1 and higher than that observed in BT-20 and MCF-7. In contrast to FGF2 which is only expressed in nonmalignant cells, no correlation between FGF1 mRNA expression and the phenotype of the cells was observed. We followed the expression of four FGF1 mRNA, heterogenous in their 5' untranslated regions. This study demonstrated that (i) the FGF1 mRNA 1.A was not expressed by mammary epithelial cells, (ii) the FGF1 mRNA 1.B was only expressed in normal mammary epithelial cells and (iii) the transcripts 1.C and 1.D were expressed in normal and malignant cells with specific patterns. The expression of FGF1 mRNAs responded in a cell specific manner to serum starvation. The mRNA 1.A was only expressed in normal cells cultured in the absence of serum while 1.C was either up- or down-regulated by serum in transformed cells and the expression of 1.D was greater in presence of serum in all cell lines. These results show that the regulation of FGF1 mRNAs expression is cell specific and does not correlate with a tumorigenic or transformed cell phenotype.

Base Sequence↗